Carbostyril derivatives

ABSTRACT

Novel carbostyril derivatives of the formula: ##STR1## wherein R 1  is H, NO 2 , alkoxy, alkoxycarbonyl, alkyl, halogen, optionally substituted amino, OH, CN, COOH, alkanoyloxy, hydrazinocarbonyl; q is 1 to 3, and R is a group of the formula: ##STR2## [wherein R 2  is H, alkoxycarbonyl, optionally substituted phenoxycarbonyl, phenylalkenyl-CO--, optionally substituted phenylalkanoyl, alkanoyl, alkenyl-CO--, optionally substituted phenyl-SO 2  --, --CONR 8  R 9 , optionally substituted heterocyclic group-CO--, naphthyl-CO--, thienylalkanoyl, tricyclo[3.3.1.1]alkanoyl, ##STR3##  (R 13  is OH, optionally substituted alkoxy, --NR 32  R 33 , --O--A--(E) l  --NR 4  R 5 , --(B) l  --NR 6  R 7 , etc.), 
     n is 1 or 2, m is 0 or 1 to 3, R 3  is alkyl, R 10  is --(CO) l  --NR 11  R 12  ], and the bond between 3- and 4-position of carbostyril nucleus is single or double bond, 
     which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

This is a continuation of application Ser. No. 07/846,941, filed Mar. 6, 1992, now abandoned, which is a divisional of application Ser. No. 07/762,736, filed Sep. 18, 1991 now U.S. Pat. No. 5,225,402, which is a continuation of application Ser. No. 07/478,181, filed Feb. 9, 1990 now abandoned.

This invention relates to novel carbostyril derivatives which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor.

The carbostyril derivatives of this invention have the following formula: ##STR4## wherein R¹ is hydrogen atom; nitro; a lower alkoxy; a lower alkoxycarbonyl; a lower alkyl; a halogen atom; an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl, benozyl and a phenyl(lower)alkoxycarbonyl; hydroxy; cyano; carboxy; a lower alkanoyloxy; or hydrazinocarbonyl,

q is an integer of 1 to 3 and

R is a group of the formula: ##STR5## wherein R² is hydrogen atom; a lower alkoxycarbonyl; a phenoxycarbonyl which phenyl ring may optionally be substituted by one to three substituents selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl and benzoyl; a phenyl(lower)alkenylcarbonyl; a phenyl(lower)alkanoyl which lower alkanoyl moiety may optionally be substituted by an amino having optionally a lower alkoxycarbonyl substituent; an alkanoyl; an alkenylcarbonyl; a phenylsulfonyl which phenyl ring may optionally be substituted by a lower alkoxy; a group of the formula: ##STR6## (wherein R⁸ and R⁹ are the same or different and are each hydrogen atom or a phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, and nitro); a heterocyclic group-substituted carbonyl which heterocyclic group may optionally have one to three substituents selected from a phenyl(lower)alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl, and a lower alkylenedioxy); a group of the formula: ##STR7## naphthylcarbonyl; thienyl(lower)alkanoyl; tricyclo[3.3.1.1]decanyl(lower)alkanoyl; tricyclo[3.3.1.1]decanylcarbonyl; or a group of the formula: ##STR8## (wherein p is 0 or an integer of 1 to 3, and R¹³ is hydroxy; an alkoxy; an alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, and a group of the formula: ##STR9## [wherein R³² and R³³ are the same or different and are each hydrogen atom, a lower alkyl, a hydroxy-substituted lower alkyl, a lower alkanoyl, a tetrahydropyranyl(lower)alkyl, phenyl, a phenyl(lower)alkyl (wherein the alkyl moiety may optionally be substituted by hydroxy and the phenyl ring may optionally be substituted by a lower alkoxy), or a pyridyl(lower)alkyl; or R³² and R³³ may bind with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be substituted by a member selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy-substituted lower alkyl)]; a carboxy-substituted alkoxy; a halogen-substituted lower alkoxy; a lower alkoxycarbonyl-substituted alkoxy; a lower alkanoyloxy-substituted lower alkoxy; a lower alkenyloxy-substituted lower alkoxy; a lower alkoxy(lower)alkoxy; a lower alkylsulfonyloxy-substituted lower alkoxy; a benzoyloxy-substituted lower alkoxy; tricyclo[3.3.1.1]decanyl-substituted lower alkoxy; a lower alkoxy(lower)alkoxy which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a lower alkyl; a morpholinyl-substituted lower alkoxy which may optionally be substituted by a lower alkyl or oxo; a benzimidazolylthio-substituted lower alkoxy; a benzimidazolylsulfinyl-substituted lower alkoxy; a group of the formula: ##STR10## (wherein A is an alkylene, l is an integer of 0 or 1, E is --CO-- or --OCO--, R⁴ and R⁵ are the same or different and are each hydrogen atom; a lower alkyl which may optionally be substituted by hydroxy or cyano; a lower alkenyl; a lower alkynyl; a phenyl(lower)alkyl; a lower alkanoyl which may optionally have one to three substituents of a halogen atom; a benzoyl which phenyl ring may optionally be substituted by a member selected from nitro and an amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl; phenyl; a lower alkoxycarbonyl; a lower alkoxycarbonyl(lower)alkyl wherein the lower alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent; an amido having optionally a lower alkyl substituent; a pyrrolidinyl-substituted carbonyl which pyrrolidinyl ring may optionally be substituted by a phenyl(lower)alkoxycarbonyl; an amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl or a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, or a phenyl(lower)alkoxycarbonyl; a hydroxy-substituted lower alkanoyl; a lower alkanoyloxy(lower)alkanoyl; a lower alkylsulfonyl; a phenylsulfonyl which phenyl ring may optionally be substituted by a lower alkyl group, nitro or an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl; an amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally hydroxy substituent, imidazolyl, carbamoyl or a lower alkylthio, and the amido group may optionally have a lower alkyl substituent; an amino-substituted lower alkyl which may optionally substituted by a lower alkyl or a lower alkanoyl; anilinocarbonyl; a piperidinyl which may optionally be substituted by a phenyl(lower)alkyl; a cycloalkyl, a cycloalkenylcarbonyl; a cycloalkylcarbonyl which may optionally have one to three substituents selected from hydroxy and a lower alkanoyloxy; a tetrahydropyranyl-substituted lower alkyl wherein the tetrahydropyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy; a lower alkanoyl which is substituted by a 5- or 6-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl and morpholinyl wherein the heterocyclic group have optionally a substituent selected from a lower alkyl and phenyl; a piperidinyl-substituted carbonyl which may optionally be substituted by a lower alkanoyl; a lower alkanoyloxy(lower)alkyl; a pyridyl-substituted lower alkyl; or an amino acid residue which can form an amido group with its amino group, or R⁴ and R⁵ may bind together with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally be substituted by a member selected from a phenyl having optionally a subsituent selected from a lower alkoxy and a halogen atom, oxo, hydroxy, a lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a lower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl); a carbamoyloxy-substituted lower alkoxy; a lower alkylthio-substituted lower alkoxy; a lower alkylsulfonyl-substituted lower alkoxy; a lower alkylsulfinyl-substituted lower alkoxy; an alkenyloxy; phenoxy; a lower alkanoyloxy; a lower alkylsulfonyloxy; a lower alkynyloxy; a phenyl(lower)alkoxy; a cycloalkyl; a cycloalkyloxy; a cycloalkenyloxy; imidazo-[4,5-c]pyridylcarbonyl(lower)alkoxy; a group of the formula: ##STR11## (wherein l is as defined above, B is a lower alkylene or a group of --CO--, and R⁶ and R⁷ are the same or different and are each hydrogen atom, a lower alkyl, a lower alkanoyl having optionally one to three halogen substituents, a carboxy(lower)alkyl, a lower alkoxycarbonyl, a lower alkoxycarbonyl(lower)alkyl, a lower alkenyl, an amido-substituted lower alkyl having optionally a lower alkyl substituent, or a phenyl(lower)alkoxycarbonyl, or R⁶ and R⁷ may bind together with nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a lower alkoxycarbonyl, a lower alkyl, a lower alkylthio, or oxo); nitro; a halogen atom; a lower alkylsulfonyl; a lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy; a cyano-substituted lower alkoxy; an oxilanyl-substituted lower alkoxy; a phthalimido-substituted alkoxy; an amidino-substituted lower alkoxy, a pyrrolyl-substituted lower alkoxy; cyano; a lower alkoxycarbonyl; amidino; carbamoyl; carboxy; a lower alkanoyl; benzoyl; a lower alkoxycarbonyl(lower)alkyl; a carboxy(lower)alkyl; a lower alkoxy(lower)alkyl; a lower alkanoyloxy(lower)alkyl; hydroxyimino-substituted lower alkyl; phenyl; a lower alkylthio; a lower alkylsulfinyl; a lower alkenyl having optionally a hydroxy substituent; a lower alkylenedioxy, a lower alkylsilyl; a pyrimidylthio-substituted lower alkoxy; a pyrimidylsulfinyl-substituted lower alkoxy; a pyrmidylsufonyl-substituted lower alkoxy; an imidazolylthio-substituted lower alkoxy which may optionally have a lower alkyl substituent; an imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent; an ammonium-lower alkoxy having three substituents selected from lower alkyl, lower alkenyl and oxo; a phenylthio-substituted lower alkoxy which phenyl ring may optionally have a substituent selected from nitro and amino; a phenylsulfonyl-substituted lower alkoxy which phenyl ring may optionally have a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl and lower alkyl; a pyridylthio-substituted lower alkoxy; or a pyridylsuflonyl-substituted lower alkoxy which pyridyl ring may optionally be substituted by oxo), n is an integer of 1 or 2, m is 0 or an integer of 1 to 3, R³ is a lower alkyl, R¹⁰ is a group of the formula: ##STR12## (wherein l is as defined above and R¹¹ and R¹² are the same or different and are each hydrogen atom, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, a benzoyl which may optionally have a lower alkoxy substituent, tricyclo[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a cycloalkyl, or R¹¹ and R¹² may bind together with nitrogen atom to which they bond to form a saturated or unsaturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom, wherein the heterocyclic group may optionally have a substituent selected from a benzoyl, a lower alkanoyl, a phenyl(lower)alkyl and a phenyl which may optionally be substituted by a lower alkoxy and a lower alkanoyl), the bond between 3- and 4-positions of the carbostyril ring is single bond or double bond, provided that when R¹ is hydrogen atom and the l in the formula: ##STR13## is 0, R¹¹ and R¹² are not simultaneously hydrogen atom.

The carbostyril derivatives of the formula (1) and their salts have excellent vasopressin antagonistic activities and vasodilating activity, hypotensive activity, activity for inhibiting saccharide release in liver, activity for inhibiting growth of mesangium cells, water diuretic activity, platelet agglutination inhibitory activity and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor and are used for the prophylaxis and treatment of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokaliemia, diabetic, circulation disorder, and the like.

Each group in the above formula (1) includes specifically the following groups.

The "lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, and the like.

The "lower alkyl" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, and the like.

The "halogen atom" includes fluorine atom, chlorine atom, bromine atom and iodine atome.

The "amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl and benzoyl" includes an amino having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and benzoyl group, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, benzoylamino, N-methyl-N-benzoylamino, N-ethyl-N-benzoylamino, and the like.

The "amino having optionally one or two substituents selected from a lower alkanoyl and a lower alkyl" includes an amino having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, and the like.

The "phenyl(lower)alkyl" includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, and the like.

The "amino having optionally one or two substituents selected from a lower alkyl, phenyl and a phenyl(lower)alkyl" includes an amino having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl and a phenylalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, amino, phenylamino, diphenylamino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-phenylamino, N-ethyl-N-phenylamino, N-benzylamino, N-(2-phenylethyl)amino, N-(1-phenylethyl)amino, N-(3-phenylpropyl)amino, N-(4-phenylbutyl)amino, N-(5-phenylpentyl)amino, N-(6-phenylhexyl)amino, N-(1,1-dimethyl-2-phenylethyl)amino, N-(2-methyl-3-phenylpropyl)amino, N-methyl-N-benzylamino, N-ethyl-N-benzylamino, N-phenyl-N-benzylamino, and the like.

The "alkoxy which has one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, and a group of the formula: ##STR14## includes an alkoxy group having 1 to 10 carbon atoms which has one or two substituents selected from hydroxy, a straight chain or branched chain alkanoyloxy having 1 to 6 carbon atoms, a trialkylammonium group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and a group of the formula: ##STR15## [wherein R³² and R³³ are the same or different and are each hydrogen atom, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a hydroxy-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a tetrahydropyranylalkyl group (wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl, a phenylalkyl wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally be substituted by hydroxy and the phenyl ring may optionally be substituted by one to three of straight chain or branched chain alkoxy group having 1 to 6 carbon atoms), or a pyridylalkyl wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms, or R³² and R³³ may bind with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom (wherein the heterocyclic group may optionally be substituted by one to three substituents selected from carbamoyl, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, phenyl and a hydroxy-substituted alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms], for example, hydroxymethoxy, 2-hydroxyethoxy, 1-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxypropoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl-2-hydroxyethoxy, 5,6-dihydroxyhexyloxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 7-hydroxyheptyloxy, 8-hydroxyoctyloxy, 9-hydroxynonyloxy, 10-hydroxydecyloxy, 6-(3,4-dimethoxybenzylamino)-5-hydroxyhexyloxy, 6-(3-methoxybenzylamino)-5-hydroxyhexyloxy, 6-[2-(2-pyridyl)ethylamino]-5-hydroxyhexyloxy, 6-[N-methyl-N-(2-pyridylethyl)amino]-5-hydroxyhexyloxy, 6-{N-ethyl-N-[2-(2-pyridyl)ethylamino]-5-hydroxyhexyloxy, 6-[N-ethyl-N-(4-pyridylmethyl)amino]-5-hydroxyhexyloxy, 6-(3-pyridylmethylamino)-5-hydroxyhexyloxy, 6-(2-pyridylmethylamino)-5-hydroxyhexyloxy, 6-(diethylmethylammonium)-5-methoxyhexyloxy, 4-(trimethylammonium)-3-hydroxyhexyloxy, 5-(dipropylethylammonium)-4-acetyloxypentyloxy, 7-(2-ethoxybenzylamino)-6-acetyloxyheptyloxy, 8-(3,4,5-trimethoxybenzylamino)-7-ethoxyoctyloxy, 5-[3-(2-pyridyl)propyl]-4-acetyloxypentyloxy, 7-[4-(3-pyridyl)butyl]-6-propoxyheptyloxy, 2-methyl-3-hydroxypropoxy, aminomethoxy, 1-aminoethoxy, 2-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, ethylaminomethoxy, propylaminomethoxy, isopropylaminomethoxy, butylaminomethoxy, tert-butylaminomethoxy, pentylaminomethoxy, hexylaminomethoxy, dimethylaminomethoxy, diethylaminomethoxy, dibutylaminomethoxy, dipentylaminomethoxy, dihexylaminomethoxy, N-methyl-N-ethylaminomethoxy, N-methyl-N-propylaminomethoxy, N-methyl-N-butylaminomethoxy, N-methyl-N-hexylaminomethoxy, 1-methylaminoethoxy, 2-ethylaminoethoxy, 3-propylaminopropoxy, 4-butylaminobutoxy, 1,1-dimethyl-2-pentylaminoethoxy, 5-hexylaminopentyloxy, 6-dimethylaminohexyloxy, 7-methylaminoheptyloxy, 8-dimethylaminooctyloxy, 4-dimethylaminobutoxy, 2-diethylaminoethoxy, 1-(N-methyl-N-hexylamino)ethoxy, 3-dihexylaminopropoxy, 6-diethylaminohexyloxy, 4-dibutylaminobutoxy, 9-(N-methyl-N-propylamino)nonyloxy, 2-(N-methyl-N-pentylamino)ethoxy, 7-hydroxy-8-dimethylaminooctyloxy, 2-hydroxy-3-diethylaminopropoxy, 7-hydroxy-8-diethylaminooctyloxy, 2-hydroxy-3-(N-phenyl-N-benzylamino)propoxy, 7-hydroxy-8-ethylaminooctyloxy, 3-hydroxy-4-methylaminobutoxy, 5-hydroxy-6-diethylaminohexyloxy, 3-hydroxy-4-phenylaminobutoxy, 8-hydroxy-9-dimethylaminononyloxy, 4-hydroxy-5-dimethylaminopentyloxy, 9-hydroxy-10-diethylaminodecyloxy, 4-hydroxy-5-methylaminopentyloxy, 4-hydroxy-5-diethylaminopentyloxy, phenylaminomethoxy, diphetnylaminomethoxy, benzylaminomethoxy, 5-hydroxy-6-benzylaminohexyloxy, 5-hydroxy-6-[N-methyl-N-(2-phenylethyl)amino]hexyloxy, 5-hydroxy-6-ethylaminohexyloxy, 5-hydroxy-6-isopropylaminohexyloxy, 5-hydroxy-6-(N-methyl-N-benzylamino)hexyloxy, 5-hydroxy-6-aminohexyloxy, (N-methyl-N-benzylamino)methoxy, (N-ethyl-N-benzylamino)methoxy, (N-phenyl-N-benzylamino)methoxy, 2-(phenylamino)ethoxy, 3-(2-phentylethylamino)propoxy, 4-(3-phenylpropylamino)butoxy, 1,1-dimethyl-2-(4-phenylbutylamino)ethoxy, 5-(5-phenylpentylamino)pentyloxy, 6-(6-phenylhexylamino)hexyloxy, 7-hydroxy-8-(N-phenyl-N-benzylamino)octyloxy, 8-hydroxy-9-[N-(2-phenylethyl)amino]nonyloxy, 9-hydroxy-10-(N-ethyl-N-benzylamino)decyloxy, acetyloxymethoxy, 2-propionyloxyethoxy, 1-butyryloxyethoxy, 3-acetyloxypropoxy, 4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy, 6-tert-butylcarbonyloxyhexyloxy, 1,1-dimethyl-2-hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy, 7-acetyloxyheptyloxy, 8-acetyloxyoctyloxy, 9-acetyloxynonyloxy, 10-acetyloxydecyloxy, (hydroxymethyl)aminomethoxy, 1-[N,N-di-(2-hydroxyethyl)amino]ethoxy, 2-(3-hydroxypropyl)aminoethoxy, 3-(4-hydroxybutyl)aminopropoxy, 4-(5-hydroxypentyl)aminobutoxy, 5-(6-hydroxyhexyl)aminopentyloxy, 6-[N-(2-hydroxyethyl)-N-methylamino]hexyloxy, 5-hydroxy-6-[N-(2-hydroxyethyl)-N-methylamino]hexyloxy, 5-hydroxy-6-[N,N-di(2-hydroxyethyl)amino]hexyloxy, 6-hydroxy-7-[N-(2-hydroxyethyl)-N-benzylamino]heptyloxy, 7-hydroxy-8-[N-(3-hydroxypropyl)-N-phenylamino]octyloxy, 7-hydroxy-9-{N-(4-hydroxybutyl)-N-[(tetrahydropyranyl-2-yl)methyl]amino}nonyloxy, 8-hydroxy-10-[N-(2-hydroxyethyl)-N-acetylamino]decyloxy, acetylaminomethoxy, 2-(formylamino)ethoxy, 1-(propionylamino)ethoxy, 3-(butyrylamino)propoxy, 4-(isobutyrylamino)butyloxy, 5-(pentanoylamino)pentyloxy, 6-(hexanoylamino)hexyloxy, 5-acetyloxy-6-acetylaminohexyloxy, 5-hydroxy-6-acetylaminohexyloxy, 6-hydroxy-7-(N-methyl-N-acetylamino)heptyloxy, 7-hydroxy-8-(N-benzyl-N-acetylamino)octyloxy, 8-hydroxy-9-(N-phenyl-N-acetylamino)nonyloxy, 9-acetyloxy-10-[N-(tetrahydropyran-2-yl)methyl-N-acetylamino]decyloxy, (tetrahydropyran-2-yl)methylaminomethoxy, 2-[(tetrahydropyran-3-yl)methylamino]ethoxy, 1-[(tetrahydropyran-4-yl)methylamino]ethoxy, 3-[2-(tetrahydropyran-2-yl)ethylamino]propoxy, 4-[3-(tetrahydropyran-2-yl)propylamino]butoxy, 5-[4-(tetrahydropyran-2-yl)butylamino]pentyloxy, 5-hydroxy-6-[N-ethyl-N-(tetrahydropyran-2-yl)methylamino]hexyloxy, 6-hydroxy-7-{N-phenyl-N-[5-(tetrahydropyran-2-yl)pentylamino}heptyloxy, 7-hydroxy-8-{N-benzyl-N-[6-(tetrahydropyran-2-yl)hexylamino}octyloxy, (2-hydroxy-2-phenylethyl)aminomethoxy, 2-[(3-hydroxy-3-phenylpropyl)amino]ethoxy, 3-[(2-hydroxy-4-phenylbutyl)amino]propoxy, 4-[(6-hydroxy-6-phenylhexyl)amino]butoxy, 5-[(2-hydroxy-2-phenylethyl)amino]pentyloxy, 5-hydroxy-6-[(2-hydroxy-2-phenylethyl)amino]hexyloxy, 6-hydroxy-7-[N-(2-hydroxy-2-phenylethyl)-N-methylamino]heptyloxy, 7-hydroxy-8-[N-(2-hydroxy-2-phenylethyl)-N-phenylamino]octyloxy, 8-hydroxy-9-[N-(2-hydroxy-2-phenylethyl)-N-benzylamino]nonyloxy, 9-hydroxy-10-[N-(2-hydroxy-2-phenylethyl)-N-acetylamino]decyloxy, (piperazin-1-yl)methoxy, 2-(pyrrolidin-1-yl)ethoxy, 3-(piperidin-1-yl)propoxy, 4-morpholinobutoxy, 5-thiomorpholinopentyloxy, 6-(piperazin-1-yl)hexyloxy, 5-hydroxy-6-(4-benzyl-1-piperazinyl)hexyloxy, 5-hydroxy-6-(1-piperazinyl)hexyloxy, 5-hydroxy-6-(4-methyl-1-piperazinyl)hexyloxy, 4-hydroxy-5-(1-pyrrolidinyl)pentyloxy, 4-hydroxy-5-(1-piperidinyl)pentyloxy, 4-hydroxy-5-morpholinopentyloxy, 5-hydroxy-6-(1-pyrrolidinyl)hexyloxy, 5-hydroxy-6-(1-piperidinyl)hexyloxy, 5-hydroxy-6-(4-phenyl-1-piperazinyl)hexyloxy, 5-hydroxy-6-(2-carbamoyl-1-pyrrolidinyl)hexyloxy, 7-hydroxy-8-(1-pyrrolidinyl)octyloxy, 5-hydroxy-6-(2-hydroxymethyl-1-pyrrolidinyl)hexyloxy, 7-(2-carbamoylmorpholino)-6-hydroxyheptyloxy, 8-hydroxy-9-(4-benzyl-1-piperazinyl)nonyloxy, 4-(3-carbamoyl-1-piperidinyl)-3-hydroxybutoxy, 9-hydroxy-10-(4-ethyl-1-piperazinyl)decyloxy, 6-(4-carbamoyl-1-piperazinyl)-5-hydroxyhexyloxy, and the like.

The "carboxy-substituted alkoxy" includes a carboxy-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, 7-carboxyheptyloxy, 8-carboxyoctyloxy, 9-carboxynonyloxy, 10-carboxydecyloxy, 11-carboxyundecyloxy, 12-carboxydodecyloxy, and the like.

The "lower alkoxycarbonyl-substituted alkoxy" includes an alkoxycarbonyl-substituted straight chain or branched chain alkoxy group having 1 to 12 carbon atoms wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarboxymethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, 7-methoxycarbonylheptyloxy, 8-ethoxycarbonyloctyloxy, 9-propoxycarbonylnonyloxy, 10-butoxycarbonyldecyloxy, 11-methoxycarbonylundecyloxy, 12-ethoxycarbonyldodecyloxy, and the like.

The "lower alkanoyloxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethoxy, 2-propionyloxyethoxy, 1-butyryloxyethoxy, 3-acetyloxypropoxy, 4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy, 6-tert-butylcarbonyloxyhexyloxy, 1,1-dimethyl-2-hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy, and the like.

The "lower alkenyloxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanyloxy group having 2 to 6 carbon atoms, for example, vinyloxymethoxy, 2-allyloxyethoxy, 1-(2-butenyloxy)ethoxy, 3-allyloxypropoxy, 4-(3-butenyloxy)butoxy, 5-(1-methylallyloxy)pentyloxy, 6-(2-pentenyloxy)hexyloxy, 1,1-dimethyl-2-(2-hexenyloxy)ethoxy, 2-methyl-3-allyloxypropoxy, and the like.

The "lower alkoxy(lower)alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethoxy, 3-methoxypropoxy, 4-ethoxybutoxy, 6-propoxyhexyloxy, 5-isopropoxypentyloxy, 1,1-dimethyl-2-butoxyethoxy, 2-methyl-3-tert-butoxypropoxy, 2-pentyloxyethoxy, hexyloxymethoxy, and the like.

The "lower alkylsulfonyloxy-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxymethoxy, 3-methylsulfonyloxypropoxy, 4-ethylsulfonyloxybutoxy, 2-methylsulfoyloxyethoxy, 6-propylsulfonyloxyhexyloxy, 5-isopropylsulfonyloxypentyloxy, 1,1-dimethyl-2-butylsulfoyloxyethoxy, 2-methyl-3-methlsulfonyloxypropoxy, and the like.

The "benzoyloxy-substituted lower alkoxy" includes a benzoyloxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzoyloxymethoxy, 2-benzoyloxyethoxy, 1-benzoyloxyethoxy, 3-benzoyloxypropoxy, 4-benzoyloxybutoxy, 6-benzoyloxyhexyloxy, 5-benzoyloxypentyloxy, 1,1-dimethyl-2-benzoyloxyethoxy, 2-methyl-3-benzoyloxypropoxy, and the like.

The "tricyclo[3.3.1.1]decanyl-substituted lower alkoxy" includes a tricyclo[3.3.1.1]decanyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, tricyclo[3.3.1.1]decanylmethoxy, 2-tricyclo[3.3.1.1]decanylethoxy, 1-tricyclo[3.3.1.1]decanylethoxy, 3-tricyclo[3.3.1.1]decanylpropoxy, 4-tricyclo[3.3.1.1]decanylbutoxy, 5-tricyclo[3.3.1.1]decanylpentyloxy, 6-tricyclo[3.3.1.1]decanylhexyloxy, 1,1-dimethyl-2-tricyclo[3.3.1.1]decanylethoxy, 2-methyl-3-tricyclo[3.3.1.1]decanylpropoxy, and the like.

The "lower alkylene" includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, and the like.

The "lower alkanoyl" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, hexanolyl, and the like.

The "amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl" includes an amino having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkoxycarbonyl group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-benzyloxycarbonylamino, N-(2-phenylethoxycarbonyl)amino, N-(1-phenylethoxycarbonyl)amino, N-(3-phenylpropoxycarbonyl)amino, N-(4-phenylbutoxycarbonyl)amino, N-(5-phenylpentyloxycarbonyl)amino, N-(6-phenylhexyloxycarbonyl)amino, N-(1,1-dimethyl-2-phenylethoxycarbonyl)amino, N-(2-methyl-3-phenylpropoxycarbonyl)amino, N-methyl-N-benzyloxycarbonylamino, N-ethyl-N-benzyloxycarbonylamino, acetylamino, formylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, N-methyl-N-acetylamino, N-ethyl-N-acetylamino, N-benzyloxycarbonyl-N-acetylamino, and the like.

The "benzoyl which phenyl ring may optionally has a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl" includes a benzoyl group which phenyl ring may optionally have one to three substituents selected from nitro and an amino having one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a phenylalkoxycarbonyl group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzoyl, 2-aminobenzoyl, 4-aminobenzoyl, 4-methylaminobenzoyl, 3-ethylaminobenzoyl, 2-(N-methyl-N-ethylamino)benzoyl, 3-(N-methyl-N-hexylamino)benzoyl, 4-dimethylaminobenzoyl, 4-dipentylaminobenzoyl, 2-isopropylaminobenzoyl, 3-butylaminobenzoyl, 4-(N-methyl-N-benzyloxycarbonylamino)benzoyl, 2-[N-(2-phenylethoxycarbonyl)amino]benzoyl, 2,3-bis(dimethylamino)benzoyl, 3,4-bis(methylamino)benzoyl, 3,4,5-tri(methylamino)benzoyl, 2,6-di(N-methyl-N-benzyloxycarbonylamino)benzoyl, 3-[N-(3-phenylpropoxycarbonyl)amino]benzoyl, 4-[N-(5-phenylpentyloxycarbonyl)amino]benzoyl, 2-[N-(6-phenylhexyloxycarbonyl)amino]benzoyl, 3-[N-(4-phenylbutoxycarbonyl)amino]benzoyl, 4-acetylaminobenzoyl, 3-(N-methyl-N-acetylamino)benzoyl, 2-(N-benzyloxycarbonyl-N-acetylamino)benzoyl, 4-nitrobenzoyl, 4-nitro-3-methylaminobenzoyl, 2,4-dinitrobenzoyl, 2,4,6-trinitrobenzoyl, and the like.

The "lower alkoxycarbonyl" includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, and the like.

The "lower alkoxycarbonyl(lower)alkyl" includes a straight chain or branched chain alkoxycarbonylalkyl group having 1 to 6 carbon atoms in the alkoxy moiety wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methoxycarbonylmethyl, 3-methoxycarbonylpropyl, ethoxycarbonylmethyl, 4-ethoxycarbonylbutyl, 1-ethoxycarbonylethyl, 1-methoxycarbonylethyl, 6-propoxycarbonylhexyl, 5-isopropoxycarbonylpentyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.

The "amido having optionally a lower alkyl substituent" includes an amido having one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoyl, methylamido, ethylamido, propylamido, isopropylamido, butylamido, tert-butylamido, pentylamido, hexylamido, dimethylamido, diethylamido, dipropylamido, dibutylamido, dipentylamido, dihexylamido, N-methyl-N-ethylamido, N-ethyl-N-propylamido, N-methyl-N-butylamido, N-methyl-N-hexylamido, and the like.

The "lower alkylsulfonyl" includes a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.

The "5- or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding the groups R⁴ and R⁵ together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, pyrazolyl, imidazolyl, imidazolidinyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, pyrrolinyl, imidazolinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, and the like.

The "phenyl which may optionally have a substituent selected from a lower alkoxy and a halogen atom" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-methoxy-3-chlorophenyl, and the like.

The "heterocyclic group which may optionally be substituted by a member selected from a phenyl having optionally a subsitutent selected from a lower alkoxy and a halogen atom, oxo, hydroxy, a lower alkenyl, carboxy, a phenyl(lower)alkyl having optionally a hydroxy substituent on the lower alkyl moiety, a lower alkanoyl, a lower alkyl having optionally a hydroxy substituent, benzoyl, an amido having optionally a lower alkyl substituent, anilinocarbonyl, a benzoyl(lower)alkyl, a lower alkylsulfonyl, piperidinyl, pyrimidinyl, pyridyl, and a lower alkoxycarbonyl" includes the above-mentioned heterocyclic group which may optionally be substituted by one to three substituents selected from a phenyl having optionally one to three subsitutents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a halogen atom, an oxo group, a hydroxy group, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, carboxy, a phenylalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally a hydroxy substituent, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally one to three hydroxy substituents, benzoyl, an amido group having optionally one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, anilinocarbonyl, a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms in the alkyl moiety, piperidinyl, pyrimidinyl, pyridyl, and a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, 4-phenylpiperazinyl, 4-(4-methoxyphenyl)piperazinyl, 4-(4-chlorophenyl)piperazinyl, 3-(2-ethoxyphenyl)pyrrolidinyl, 2-(4-isopropoxyphenyl)pyrrolidinyl, 4-(4-pentyloxyphenyl)piperidinyl, 3-(4-hexyloxyphenyl)piperidinyl, 3-(2,3-dimethoxyphenyl)morpholino, 2-(2-methoxyphenyl)morpholino, 3-(3-ethoxyphenyl)thiomorpholino, 2-(3,4,5-trimethoxyphenyl)thiomorpholino, 4-(3,4-dimethoxyphenyl)piperazinyl, 4-(3,4,5-trimethoxyphenyl)piperazinyl, 3-(2-fluorophenyl)pyrrolidinyl, 2-(3-bromophenyl)pyrrolidinyl, 4-(3-iodophenyl)piperidinyl, 3-(4-bromophenyl)piperidinyl, 2-(3,4-dichlorophenyl)morpholino, 3-(3-chlorophenyl)morpholino, 3-(2-bromophenyl)thiomorpholino, 2-(4-fluorophenyl)thiomorpholino, 4-(3,4,5-trichlorophenyl)piperazinyl, 4-(2,6-dichlorophenyl)piperazinyl, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4-phenylbutyl)piperidinyl, 3-(5-phenylpentyl)morpholino, 2-(6-phenylhexyl)thiomorpholino, 4-(2-phenyl-2-hydroxyethyl)piperazinyl, 3-(1-hydroxy-1-phenylmethyl)pyrrolidinyl, 2-(3-hydroxy-3-phenylpropyl)pyrrolidinyl, 4-(2-hydroxy-4-phenylbutyl)piperidinyl, 2-(5-hydroxy-5-phenylpentyl)thiomorpholino, 3-(6-hydroxy-6-phenylhexyl)morpholino, 4-acetylpiperazinyl, 3-formylpyrrolidinyl, 2-propionylpyrrolidinyl, 4-butyrylpiperidinyl, 3-pentanoylthiomorpholino, 2-hexanoylmorpholino, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 2-hexylthiomorpholino, 4-benzoylpiperazinyl, 3-benzoylpyrrolidinyl, 3-benzoylmorpholino, 2-benzoylthiomorpholino, 3-benzoylpiperidinyl, 4-anilinocarbonylpiperazinyl, 2-anilinocarbonylpyrrolidinyl, 3-anilinocarbonylpiperidinyl, 2-anilinocarbonylmorpholino, 3-anilinocarbonylthiomorpholino, 4-(benzoylmethyl)piperazinyl, 3-(1-benzoylethyl)pyrrolidinyl, 2-(3-benzoylpropyl)pyrrolidinyl, 4-(4-benzoylbutyl)piperidinyl, 3-(5-benzoylpentyl)morpholino, 2-(6-benzoylhexyl)thiomorpholino, 3-methyl-4-benzoylpiperazinyl, 3-ethyl-4-acetylpiperidinyl, 3-methyl-4-benzylpyrrolidinyl, 3-propyl-4-anilinocarbonylpyrrolidinyl, 3-methyl-5-(benzoylmethyl)morpholino, 3-methyl-5-(2-phenyl-2-hydroxyethyl)thiomorpholino, 4-methylsulfonylpiperazinyl, 4-methoxycarbonylpiperazinyl, 3-ethylsulfonylpyrrolidinyl, 3-ethoxycarbonylpyrrolidinyl, 4-propylsulfonylpiperidinyl, 3-propoxycarbonylpiperidinyl, 3-butylsulfonylmorpholino, 2-pentyloxycarbonylmorpholino, 2-hexylsulfonylthiomorpholino, 3-hexyloxycarbonylthiomorpholino, 4-allylpiperazinyl, 4-ethoxycarbonylpiperidinyl, 4-carboxypiperidinyl, 4-dimethylamidopiperidinyl, 4-carbamoylpiperidinyl, 4-(1-piperidinyl)piperidinyl, 3-hydroxypiperidinyl, 2-carbamoylpyrrolidinyl, 2-hydroxymethylpiperidinyl, 2-hydroxymethylpyrrolidinyl, 3-hydroxymethylpiperidinyl, 3-hydroxypyrrolidinyl, 4-(2-hydroxyethyl)piperidinyl, 2-methoxycarbonylpyrrolidinyl, 2-(2-hydroxyethyl)piperidinyl, (2-pyrimidyl)piperazinyl, (2-pyridyl)piperazinyl, 2-methylimidazolyl, 3-methyl-1,2,4-triazolyl, 5-methyl-1,2,3,4-tetrazolyl, 4-hydroxymethylimidazolyl, 3-allyl-1,2,4-triazolyl, 5-phenyl-1,2,3,4-tetrazolyl, 3-carboxypyrrolyl, 2-hydroxyoxazolidinyl, 2-carbamoylthiazolidinyl, 4-oxothiomorpholino, 4,4-dioxothiomorpholino, and the like.

The "phenyl(lower)alkyl having optionally a hydroxy-substituent on the alkyl moiety and having optionally a lower alkoxy substituent on the phenyl ring" includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally a hydroxy-substituent and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the above-mentioned phenyl(lower)alkyl groups, 1-hydroxy-1-phenylmethyl, 1-phenyl-2-hydroxyethyl, 2-phenyl-2-hydroxyethyl, 3-hydroxy-3-phenylpropyl, 2-hydroxy-4-phenylbutyl, 6-hydroxy-6-phenylhexyl, 3,4-dimethoxybenzyl, 3-methoxybenzyl, 1-(2-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 3-(2-ethoxyphenyl)propyl, 4-(3-ethoxyphenyl)butyl, 5-(4-ethoxyphenyl)pentyl, 6-(4-isopropoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3-ethoxy-4-methoxybenzyl, 2,3-dimethoxybenzyl, 3,4-diethoxybenzyl, 3,4,5-trimethoxybenzyl, 1-hydroxy-1-(3-methoxyphenyl)methyl, 1-(2,5-dimethoxyphenyl)-2-hydroxyethyl, 2-(2,6-dimethoxyphenyl)-2-hydroxyethyl, 5-hydroxy-5-(3,4-dipentyloxyphenyl)pentyl, and the like.

The "benzoyl(lower)alkyl" includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoylmethyl, 1-benzoylethyl, 2-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, and the like.

The "carbamoyloxy-substituted lower alkoxy" includes a carbamoyloxy-substituted alkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carbamoyloxymethoxy, 2-carbamoyloxyethoxy, 1-carbamoyloxyethoxy, 3-carbamoyloxypropoxy, 4-carbamoyloxybutoxy, 5-carbamoyloxypentyloxy, 6-carbamoyloxyhexyloxy, 1,1-dimethyl-2-carbamoyloxyethoxy, 2-methyl-3-carbamoyloxypropoxy, and the like.

The "lower alkylthio-substituted alkoxy" includes a alkylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms wherein the alkylthio moiety is a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthiomethoxy, 3-ethylthiopropoxy, 4-methylthiobutoxy, 2-methylthioethoxy, 6-propylthiohexyloxy, 5-isopropylthiopentyloxy, 1,1-dimethyl-2-butylthioethoxy, 2-methyl-3-methylthiopropoxy, and the like.

The "lower alkylsulfonyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, methylsulfonylmethoxy, 3-ethylsulfonylpropoxy, 4-methylsulfonylbutoxy, 2-methylsulfoylethoxy, 6-propylsulfonylhexyloxy, 5-isopropylsulfonylpentyloxy, 1,1-dimethyl-2-butylsulfoylethoxy, 2-methyl-3-methylsulfonylpropoxy, and the like.

The "lower alkylsulfinyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinylmethoxy, 3-ethylsulfinylpropoxy, 4-methylsulfinylbutoxy, 2-methylsulfinylethoxy, 6-propylsulfinylhexyloxy, 5-isopropylsulfinylpentyloxy, 1,1-dimethyl-2-butylsulfinylethoxy, 2-methyl-3-methylsulfinylpropoxy, and the like.

The "lower alkenyloxy" includes a straight chain or branched chain alkenyl group having 2 to 12 carbon atoms and containing one to three double bonds, for example, vinyloxy, allyloxy, 3-methyl-2-butenyloxy, 2-butenyloxy, 3-butenyloxy, 1-methylallyloxy, 2-pentenyloxy, 2-hexenyloxy, 1-heptenyloxy, 1-octenyloxy, 1-nonenyloxy, 1-decenyloxy, 1-undecenyloxy, 1-dodecenyloxy, 2-heptenyloxy, 3-heptenyloxy, 2-methyl-4-heptenyloxy, 2-methyl-5-heptenyloxy, 4-methyl-2-heptenyloxy, 3-methyl-1-heptenyloxy, 1,3-heptadienyloxy, 1,4-heptadienyloxy, 1,5-heptadienyloxy, 1,6-heptadienyloxy, 2,4-heptadienyloxy, 2-methyl-2,4-heptadienyloxy, 2,6-dimethyl-2,4-heptadienyloxy, 2,5-dimethyl-1,3-heptadienyloxy, 2,4,6-trimethyl-2,4-heptadienyloxy, 2-octenyloxy, 3-octenyloxy, 4-octenyloxy, 2-methyl-5-octenyloxy, 2-methyl-6-octenyloxy, 2-methyl-7-octenyloxy, 1,3-octadienyloxy, 1,4-octadienyloxy, 1,5-octadienyloxy, 1,6-octadienyloxy, 1,7-octadienyloxy, 2,4-octadienyloxy, 3,7-octadienyloxy, 4,8-dimethyl-3,7-octadienyloxy, 2,4,6-trimethyl-3,7-octadienyloxy, 3,4-dimethyl-2,5-octadienyloxy, 3,7-dimethyl-2,6-octadienyloxy, 4,8-dimethyl-2,6-octadienyloxy, 2-nonenyloxy, 3-nonenyloxy, 4-nonenyloxy, 2-methyl-5-nonenyloxy, 2-methyl-6-nonenyloxy, 2-methyl-7-nonenyloxy, 2-methyl-8-nonenyloxy, 1,3-nonadienyloxy, 1,4-nonadienyloxy, 1,5-nonadienyloxy, 1,6-nonadienyloxy, 1,7-nonadienyloxy, 1,8-nonadienyloxy, 2,4-nonadienyloxy, 3,7-nonadienyloxy, 4,8-dimethyl-3,7-nonadienyloxy, 2,4,6-trimethyl-3,7-nonadienyloxy, 3,4-dimethyl-2,5-nonadienyloxy, 4,8-dimethyl-2,6-nonadienyloxy, 2-decenyloxy, 3-decenyloxy, 4-decenyloxy, 5-decenyloxy, 2-methyl-6-decenyloxy, 3-methyl-7-decenyloxy, 4-methyl-8-decenyloxy, 5-methyl-9-decenyloxy, 1,3-decadienyloxy, 1,4-decadienyloxy, 1,5-decadienyloxy, 1,6-decadienyloxy, 1,7-decadienyloxy, 1,8-decadienyloxy, 1,9-decadienyloxy, 2-methyl-2,4-decadienyloxy, 3-methyl-2,5-decadienyloxy, 4,8-dimethyl-2,6-decadienyloxy, 2,4,6-trimethyl-3,7-decadienyloxy, 2,9-dimethyl-3,7-decadienyloxy, 2-undecenyloxy, 3-undecenyloxy, 4-undecenyloxy, 5-undecenyloxy, 2-methyl-6-undecenyloxy, 3-methyl-7-undecenyloxy, 4-methyl-8-undecenyloxy, 5-methyl-9-undecenyloxy, 2-methyl-10-undecenyloxy, 1,3-undecadienyloxy, 1,4-undecadienyloxy, 1,5-undecadienyloxy, 1,6-undecadienyloxy, 1,7-undecadienyloxy, 1,8-undecadienyloxy, 1,9-undecadienyloxy, 1,10-undecadienyloxy, 2-methyl-2,4-undecadienyloxy, 3-methyl-2,5-undecadienyloxy, 4,8-dimethyl-2,6-undecadienyloxy, 2,4,6-trimethyl-3,8-undecadienyloxy, 2,9-dimethyl-3,8-undecadienyloxy, 2-dodecenyloxy, 3-dodecenyloxy, 4-dodecenyloxy, 5-dodecenyloxy, 6-dodecenyloxy, 2-methyl-7-dodecenyloxy, 3-methyl-8-dodecenyloxy, 4-methyl-9-dodecenyloxy, 5-methyl-10-dodecenyloxy, 6-methyl-11-dodecenyloxy, 2-methyl-2,4-dodecadienyloxy, 3-methyl-2,5-dodecadienyloxy, 4,8-dimethyl-2,6-dodecadienyloxy, 2,4,6-trimethyl-2,7-dodecadienyloxy, 2,10-dimethyl-2,8-dodecadienyloxy, 2,5-dimethyl-3,7-dodecadienyloxy, 4,8,12-trimethyl-3,7,11-dodecatrienyloxy, 1,3,5-heptatrienyloxy, 2,4,6-octatrienyloxy, 1,3,6-nonatrienyloxy, 2,6,8-dodecatrienyloxy, 1,5,7-undecatrienyloxy, and the like.

The "lower alkanoyloxy" includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy, hexanoyloxy, and the like.

The "lower alkylsulfonyloxy" includes a straight chain or branched chain alkylsulfonyloxy group having 1 to 6 carbon atoms, for example, methylsulfonyloxy, ethylsulfonyloxy, isopropylsulfonyloxy, butylsulfoyloxy, tert-butylsulfonyloxy, pentylsulfonyloxy, hexylsulfonyloxy, and the like.

The "lower alkynyloxy" includes a straight chain or branched chain alkynyloxy group having 2 to 6 carbon atoms, for example, ethynyloxy, 2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-propynyloxy, 2-pentynyloxy, 2-hexynyloxy, and the like.

The "phenyl(lower)alkoxy" includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy, and the like.

The "cycloalkyloxy" includes a cycloalkyloxy group having 3 to 8 carbon atoms, for example, cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, and the like.

The "cycloalkenyloxy" includes a cycloalkenyloxy group having 3 to 8 carbon atoms, for example, cyclopropenyloxy, cyclobutenyloxy, cyclopentenyloxy, cyclohexenyloxy, cycloheptenyloxy, cyclooctenyloxy, and the like.

The "lower alkanoyl which may optionally have one to three substituents of a halogen atom" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have one to three substituents of a halogen atom, for example, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichlopropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.

The "lower alkenyl" includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.

The "lower alkylthio" includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.

The "5- or 6-membered, saturated or unsaturated heterocyclic group which is formed by binding R⁶ and R⁷ together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, pyrazolyl, imidazolyl, imidazolidinyl, pyrrolyl, imidazolinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, and the like.

The "heterocyclic group having a substituent selected from a lower alkoxycarbonyl, lower alkyl, lower alkylthio or oxo" includes the above heterocyclic groups which have a substituent selected from a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, and an oxo group, for example, 4-tert-butoxycarbonylpiperazinyl, 4-methylpiperazinyl, 2-ethylthioimidazolyl, 2-oxopyrrolidinyl, 2-oxo-oxazolidinyl, 3-oxopiperazinyl, 4-methoxycarbonylpiperazinyl, 3-ethoxycarbonylpiperidinyl, 2-propoxycarbonylpyrrolidinyl, 3-pentyloxycarbonylthiomorpholino, 2-hexyloxycarbonylthiomorpholino, 3-ethoxycarbonylpyrrolyl, 3-methoxycarbonylimidazolyl, 3-ethylpiperidinyl, 3-propylpyrrolidinyl, 3-butylpyrrolyl, 2-pentylimidazolyl, 3-hexylmorpholino, 2-methylthiomorpholino, 2-methyloxazolidinyl, 2-ethylthiazolinyl, 3-methylisoxazolinyl, 2-methylthioimidazolyl, 2-propylthioimidazolinyl, 2-butylthioimidazolidinyl, 3-pentylthiopyrrolyl, 3-hexylthiopyrrolinyl, 3-methylthiopyrrolidinyl, 3-ethylthiomorpholino, 2-methylthiomorpholino, 2-methylthioisoxazalidinyl, and the like.

The "lower alkyl which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a lower alkoxy" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have one to three substituents selected from a halogen atom, hydroxy, phenyl and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the above-mentioned lower alkyl groups, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihyroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl,-6-phenylhexyl, 2-methyl-3-phenylpropyl, methoxymethyl, 3-methoxypropyl, 4-ethoxybutyl, 6-propoxyhexyl, 5-isopropoxypentyl, 1,1-dimethyl-2-butoxyethyl, 2-methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, dimethoxymethyl, 2,3-dimethoxyethyl, 6,6,5-trimethoxyhexyl, 1-hydroxy-1-phenylmethyl, 1-hydroxy-2-phenylethyl, 1-hydroxy-3-phenylpropyl, 1-methoxy-1-phenylmethyl, and the like.

The "cyano-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by cyano group, for example, cyanomethoxy, 2-cyanoethoxy, 1-cyanoethoxy, 3-cyanopropoxy, 4-cyanobutoxy, 5-cyanopentyloxy, 6-cyanohexyloxy, 1,1-dimethyl-2-caynoethoxy, 2-methyl-3-cyanopropoxy, and the like.

The "oxilanyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by oxilanyl group, for example, glycidoxy, 2-oxilanylethoxy, 1-oxilanylethoxy, 3-oxilanylpropoxy, 4-oxilanylbutoxy, 5-oxilanylpentyloxy, 6-oxilanylhexyloxy, 1,1-dimethyl-2-oxilanylethoxy, 2-methyl-3-oxilanylpropoxy, and the like.

The "phthalimido-substituted alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 12 carbon atoms which is substituted by phthalimido group, for example, phthalimidomethoxy, 2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy, 1,1-dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, 7-phthalimidoheptyloxy, 8-phthalimidooctyloxy, 9-phthalimidononyloxy, 10-phthalimidodecyloxy, 11-phthalimidoundecyloxy, 12-phthalimidododecyloxy, and the like.

The "pyrrolyl-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by pyrrolyl group, for example, (1-pyrrolyl)methoxy, 2-(2-pyrrolyl)ethoxy, 1-(3-pyrrolyl)ethoxy, 3-(1-pyrrolyl)propoxy, 4-(1-pyrrolyl)butoxy, 5-(2-pyrrolyl)pentyloxy, 6-(3-pyrrolyl)hexyloxy, 1,1-dimethyl-2-(1-pyrrolyl)ethoxy, 2-methyl-3-(1-pyrrolyl)propoxy, and the like.

The "amidino-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by amidino group, for example, amidinomethoxy, 2-amidinoethoxy, 1-amidinoethoxy, 3-amidinopropoxy, 4-amidinobutoxy, 5-amidinopentyloxy, 6-amidinohexyloxy, 1,1-dimethyl-2-amidinoethoxy, 2-methyl-3-amidinopropoxy, and the like.

The "lower alkanoyloxy(lower)alkyl" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyloxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.

The "lower alkylsulfinyl" includes a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, butylsulfiyl, tert-butylsulfinyl, pentylsulfinyl, hexylsulfinyl, and the like.

The "lower alkenyl having optionally a hydroxy-substituent" include a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms and having optionally a hydroxy-substituent, for example, in addition to the above-mentioned alkenyl groups, 1-hydroxyallyl, 4-hydroxy-1-butenyl, 4-hydroxy-2-butenyl, 2-hydroxy-3-butenyl, 5-hydroxy-2-pentenyl, 6-hydroxy-2-hexenyl, and the like.

The "lower alkylenedioxy" includes a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, methylenedioxy, ethylenedioxy, trimethylenedioxy, tetramethylenedioxy, and the like.

The lower alkylsilyl includes a silyl group having one to three substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylsilyl, ethylsilyl, propylsilyl, isopropylsilyl, butylsilyl, tert-butylsilyl, pentylsilyl, hexylsilyl, dimethylsilyl, trimethylsilyl, dimethyl-tert-butylsilyl, and the like.

The "amino which may optionally substituted by a lower alkanoyl" includes an amino which may optionally substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

The "phenoxycarbonyl which may optionally have one to three substituents selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl, lower alkyl and benzoyl" includes a phenoxycarbonyl group which may optionally have one to three substituents selected from nitro group and an amino group having optionally one or two substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and benzoyl group, for example, phenoxycarbonyl, 2-nitrophenoxycarbonyl, 3-nitrophenoxycarbonyl, 4-nitrophenoxycarbonyl, 3,4-dinitrophenoxycarbonyl, 2,5-dinitrophenoxycarbonyl, 2,6-dinitrophenoxycarbonyl, 3,4,5-trinitrophenoxycarbonyl, 2-aminophenoxycarbonyl, 3-aminophenoxycarbonyl, 4-aminophenoxycarbonyl, 3-acetylaminophenoxycarbonyl, 4-formylaminophenoxycarbonyl, 4-isobutyrylaminophenoxycarbonyl, 2-pentanoylaminophenoxycarbonyl, 3-hexanoylaminophenoxycarbonyl, 3,4-diacetylaminophenoxycarbonyl, 3,4-diaminophenoxycarbonyl, 2,6-diaminophenoxycarbonyl, 2,5-diaminophenoxycarbonyl, 2,4,6-triaminophenoxycarbonyl, 4-acetylaminophenoxycarbonyl, 4-dimethylaminophenoxycarbonyl, 4-benzoylaminophenoxycarbonyl, 3-(N-methyl-N-benzoylamino)phenoxycarbonyl, 2-(N-ethyl-N-acetylamino)phenoxycarbonyl, and the like.

The "phenyl(lower)alkenylcarbonyl" includes a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms, for example, cinnamoyl, 4-phenyl-3-butenoyl, 4-phenyl-2-butenoyl, 5-phenyl-4-pentenoyl, 5-phenyl-3-pentenoyl, 5-phenyl-2-pentenoyl, 6-phenyl-5-hexenoyl, 6-phenyl-4-hexenoyl, 6-phenyl-3-hexenoyl, 6-phenyl-2-hexenoyl, 2-methyl-4-phenyl-3-butenoyl, and the like.

The "amino having optionally a lower alkoxycarbonyl substituent" includes an amino being optionally substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, hexyloxycarbonylamino, and the like.

The "phenyl(lower)alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by an amino having optionally a lower alkoxycarbonyl substituent" includes a phenylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms and may optionally be substituted by an amino group which may optionally be substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, 3-methyl-4-phenylbutyryl, 2-amino-4-phenylacetyl, 2-tert-butoxycarbonylamino-2-phenylacetyl, 2-methoxycarbonylamino-2-phenylacetyl, 2-ethoxycarbonylamino-3-phenylpropionyl, 2-propoxycarbonylamino-4-phenylbutyryl, 2-pentyloxycarbonylamino-5-phenylpentanoyl, 2-hexyloxycarbonylamino-6-phenylhexanoyl, and the like.

The "alkanoyl" includes a straight chain or branched chain alkanoyl group having 1 to 12 carbon atoms, for example, in addition to the above-mentioned lower alkanoyl groups, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, neopentanoyl, and the like.

The "alkenylcarbonyl" includes a straight chain or branched chain alkenylcarbonyl group having 2 to 12 carbon atoms and having one to three double bonds, for example, vinylcarbonyl, acrylcarbonyl, 3-methyl-2-butenylcarbonyl, 2-butenylcarbonyl, 1-methylallylcarbonyl, 2-pentenylcarbonyl, 2-hexenylcarbonyl, 1-heptenylcarbonyl, 1-octenylcarbonyl, 1-nonenylcarbonyl, 1-decenylcarbonyl, 1-undecenylcarbonyl, 1-dodecenylcarbonyl, 2-heptenylcarbonyl, 3-heptenylcarbonyl, 2-methyl-4-heptenylcarbonyl, 2-methyl-5-heptenylcarbonyl, 4-methyl-2-heptenylcarbonyl, 3-methyl-1-heptenylcarbonyl, 1,3-heptadienylcarbonyl, 1,4-heptadienylcarbonyl, 1,5-heptadienylcarbonyl, 1,6-heptadienylcarbonyl, 2,4-heptadienylcarbonyl, 2-methyl-2,4-heptadienylcarbonyl, 2,6-dimethyl-2,4-heptadienylcarbonyl, 2,6-dimethyl-1,5-heptadienylcarbonyl, 2,5-dimethyl-1,3-heptadienylcarbonyl, 2,4,6-trimethyl-2,4-heptadienylcarbonyl, 2-octenylcarbonyl, 3-octenylcarbonyl, 4-octenylcarbonyl, 2-methyl-5-octenylcarbonyl, 2-methyl-6-octenylcarbonyl, 2-methyl-7-octenylcarbonyl, 1,3-octadienylcarbonyl, 1,4-octadienylcarbonyl, 1,5-octadienylcarbonyl, 1,6-octadienylcarbonyl, 1,7-octadienylcarbonyl, 2,4-octadienylcarbonyl, 3,7-octadienylcarbonyl, 4,8-dimethyl-3,7-octadienylcarbonyl, 2,4,6-trimethyl-3,7-octadienylcarbonyl, 3,4-dimethyl-2,5-octadienylcarbonyl, 4,8-dimethyl-2,6-octadienylcarbonyl, 2-nonenylcarbonyl, 3-nonenylcarbonyl, 4-nonenylcarbonyl, 2-methyl-5-nonenylcarbonyl, 2-methyl-6-nonenylcarbonyl, 2-methyl-7-nonenylcarbonyl, 2-methyl-8-nonenylcarbonyl, 1,3-nonadienylcarbonyl, 1,4-nonadienylcarbonyl, 1,5-nonadienylcarbonyl, 1,6-nonadienylcarbonyl, 1,7-nonadienylcarbonyl, 1,8-nonadienylcarbonyl, 2,4-nonadienylcarbonyl, 3,7-nonadienylcarbonyl, 4,8-dimethyl-3,7-nonadienylcarbonyl, 2,4,6-trimethyl-3,7-nonadienylcarbonyl, 3,4-dimethyl-2,5-nonadienylcarbonyl, 4,8-dimethyl-2,6-nonadienylcarbonyl, 2-decenylcarbonyl, 3-decenylcarbonyl, 4-decenylcarbonyl, 5-decenylcarbonyl, 2-methyl-6-decenylcarbonyl, 3-methyl-7-decenylcarbonyl, 4-methyl-8-decenylcarbonyl, 5-methyl-9-decenylcarbonyl, 1,3-decadienylcarbonyl, 1,4-decadienylcarbonyl, 1,5-decadienylcarbonyl, 1,6-decadienylcarbonyl, 1,7-decadienylcarbonyl, 1,8-decadienylcarbonyl, 1,9-decadienylcarbonyl, 2-methyl-2,4-decadienylcarbonyl, 3-methyl-2,5-decadienylcarbonyl, 4,8-dimethyl-2,6-decadienylcarbonyl, 2,4,6-trimethyl-3,7-decadienylcarbonyl, 2,9-dimethyl-3,7-decadienylcarbonyl, 2-undecenylcarbonyl, 3-undecenylcarbonyl, 4-undecenylcarbonyl, 5-undecenylcarbonyl, 2-methyl-6-undecenylcarbonyl, 3-methyl-7-undecenylcarbonyl, 4-methyl-8-undecenylcarbonyl, 5-methyl-9-undecenylcarbonyl, 2-methyl-10-undecenylcarbonyl, 1,3-undecadienylcarbonyl, 1,4-undecadienylcarbonyl, 1,5-undecadienylcarbonyl, 1,6-undecadienylcarbonyl, 1,7-undecadienylcarbonyl, 1,8-undecadienylcarbonyl, 1,9-undecadienylcarbonyl, 1,10-undecadienylcarbonyl, 2-methyl-2,4-undecadienylcarbonyl, 3-methyl-2,5-undecadienylcarbonyl, 4,8-dimethyl-2,6-undecadienylcarbonyl, 2,4,6-trimethyl-3,8-undecadienylcarbonyl, 2,9-dimethyl-3,8-undecadienylcarbonyl, 2-dodecenylcarbonyl, 3-dodecenylcarbonyl, 4-dodecenylcarbonyl, 5-dodecenylcarbonyl, 6-dodecenylcarbonyl, 2-methyl-7-dodecenylcarbonyl, 3-methyl-8-dodecenylcarbonyl, 4-methyl-9-dodecenylcarbonyl, 5-methyl-10-dodecenylcarbonyl, 6-methyl-11-dodecenylcarbonyl, 2-methyl-2,4-dodecadienylcarbonyl, 3-methyl-2,5-dodecadienylcarbonyl, 4,8-dimethyl-2,6-dodecadienylcarbonyl, 2,4,6-trimethyl-2,7-dodecadienylcarbonyl, 2,10-dimethyl-2,8-dodecadienylcarbonyl, 2,5-dimethyl-3,7-dodecadienylcarbonyl, 4,8,12-trimethyl-3,7,11-dodecatrienylcarbonyl, 1,3,5-heptatrienylcarbonyl, 2,4,6-octatrienylcarbonyl, 1,3,6-nonatrienylcarbonyl, 2,6,8-dodecatrienylcarbonyl, 1,5,7-undecatrienylcarbonyl, and the like.

The "phenylsulfonyl which phenyl ring may optionally have a lower alkoxy substituent" includes a phenylsulfonyl group which phenyl ring may optionally have one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methoxyphenylsulfonyl, 3-methoxyphenylsulfonyl, 4-methoxyphenylsulfonyl, 2-ethoxyphenylsulfonyl, 3-ethoxyphenylsulfonyl, 4-ethoxyphenylsulfonyl, 4-isopropoxyphenylsulfonyl, 4-pentyloxyphenylsulfonyl, 4-hexyloxyphenylsulfonyl, 3,4-dimethoxyphenylsulfonyl, 3-ethoxy-4-methoxyphenylsulfonyl, 2,3-dimethoxyphenylsulfonyl, 3,4-diethoxyphenylsulfonyl, 2,5-dimethoxyphenylsulfonyl, 2,6-dimethoxyphenylsulfonyl, 3,5-dimethoxyphenylsulfonyl, 3,4-dipentyloxyphenylsulfonyl, 3,4,5-trimethoxyphenylsulfonyl, and the like.

The "phenyl which may optionally have one to three substituents selected from a lower alkoxy, a lower alkyl, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, and nitro" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a halogen atom, an amino group having optionally one or two substituents selected from straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, and a nitro group, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 3,4-dinitrophenyl, 2,5-dinitrophenyl, 2,6-dinitrophenyl, 3,4,5-trinitrophenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 3-(N-acetylamino)phenyl, 4-(N-formylamino)phenyl, 4-(N-isobutyrylamino)phenyl, 2-(N-pentanoylamino)phenyl, 3,4-diaminophenyl, 3,4-di(N-acetylamino)phenyl, 3,4,5-triaminophenyl, 2,6-diaminophenyl, 2,5-diaminophenyl, 3,5-di-t-butyl-4-hydroxyphenyl, 3-hydroxy-4-pentyloxyphenyl, 2-hydroxy-5-t-butylphenyl, 3,5-dichloro-4-aminophenyl, 3-amino-4-hydroxyphenyl, 3-acetylamino-4-methoxyphenyl, 3-nitro-4-acetylaminophenyl, 3-nitro-4-chlorophenyl, 3-chloro-4-methylphenyl, 3-methoxy-4-methyl-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl, 3,5-diiodo-4-methoxyphenyl, 4-dimethylaminophenyl, 3-methylaminophenyl, 2-butylaminophenyl, 4-diethylaminophenyl, 3-dipropylaminophenyl, 2-(N-methyl-N-hexaylamino)phenyl, 4-(N-methyl-N-acetylamino)phenyl, 2,4-dimethylaminophenyl, and the like.

The "heterocyclic group-substituted carbonyl" includes a 5- to 10-membered, monocyclic or dicyclic heterocyclic groups containing one or two hetero atoms selected from nitrogen atom, oxygen atom and/or sulfur atom, for example, 2-pyrrolidinylcarbonyl, 3-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, 1-piperazinylcarbonyl, morpholinocarbonyl, thiomopholinocarbonyl, 2-tetrahydrofurylcarbonyl, 2-thienylcarbonyl, 3-thienylcarbonyl, 2-pyrrolylcarbonyl, 3-pyrrolylcarbonyl, 2-furoyl, 3-furoyl, 2-pyridylcarbonyl, 3-pyridylcarbonyl, 4-pyridylcarbonyl, 3-pyridazylcarbonyl, 2-thiazolylcarbonyl, 2-oxazolylcarbonyl, 2-imidazolylcarbonyl, 4-pyridazylcarbonyl, 5-pyridazylcarbonyl, 6-pyridazylcarbonyl, 2-pyrimidylcarbonyl, 4-pyrimidylcarbonyl, 5-pyrimidylcarbonyl, 6-pyrimidylcarbonyl, 2-pyradylcarbonyl, 3-pyradylcarbonyl, 6-quinolylcarbonyl, 5-indolylcarbonyl, 6-isoquinolylcarbonyl, 4-cinnolylcarbonyl, 3-quinoxalylcarbonyl, 4-phthalazylcarbonyl, 3-benzo[b]furanylcarbonyl, 5-benzo[b]thiophenylcarbonyl, 2-oxo-6-quinolylcarbonyl, 2-oxo-4-quinolylcarbonyl, and the like.

The above "heterocyclic group-substituted carbonyl which has one to three substitutents selected from a phenyl(lower)alkoxycarbonyl, a phenyl(lower)alkoxy, oxo, a lower alkyl and a lower alkylenedioxy" includes the above-mentioned heterocyclic group-substituted carbonyl groups which have one to three substituents selected from a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, an oxo group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a straight chain or branched chain alkylenedioxy group having 1 to 4 carbon atoms, for example, 1-benzyloxycarbonyl-2-pyrrolidinylcarbonyl, 3-benzyloxycarbonyl-4,5-(1,1-dimethylmethylene)-2-tetrahydrofurylcarbonyl, 4-(2-phenylethoxycarbonyl)-1-piperazinylcarbonyl, 3-methyl-2-thienylcarbonyl, 3-ethyl-2-pyrrolylcarbonyl, 3-propyl-2-furoyl, 4-butyl-2-oxo-6-quinolylcarbonyl, 6-pentyl-2-oxo-4-quinolylcarbonyl, 5-hexyl-2-pyrazylcarbonyl, 1,3-dioxo-2-methyl-6-quinazolylcarbonyl, 4,5-methylenedioxy-3-indolylcarbonyl, 3-(3-phenylpropoxy)morpholinocarbonyl, and the like.

The "thienyl(lower)alkanoyl" includes a thienylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-(2-thienyl)acetyl, 3-(3-thienyl)propionyl, 2-(3-thienyl)propionyl, 4-(2-thienyl)butyryl, 2,2-dimethyl-3-(3-thienyl)propionyl, 5-(2-thienyl)pentanoyl, 6-(3-thienyl)hexanoyl, 3-methyl-4-(2-thienyl)butyryl, and the like.

The "tricyclo[3.3.1.1]decanyl(lower)alkanoyl" includes a tricyclo[3.3.1.1]decanylalkanoyl wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-tricyclo[3.3.1.1]decanylacetyl, 3-tricyclo[3.3.1.1]decanylpropionyl, 2-tricyclo[3.3.1.1]decanylpropionyl, 4-tricyclo[3.3.1.1]decanylbutyryl, 2,2,-dimethyl-3-tricyclo[3.3.1.1]decanylpropionyl, 5-tricyclo[3.3.1.1]decanylpentanoyl, 6-tricyclo[3.3.1.1]decanylhexanoyl, 3-methyl-4-tricyclo[3.3.1.1]decanylbutyryl, and the like.

The "benzoyl which phenyl ring may optionally have a lower alkoxy substituent" includes a benzoyl which may optionally have one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, benzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-butoxybenzoyl, 4-isopropoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-dimethoxybenzoyl, 3-ethoxy-4-methoxybenzoyl, 2,3-dimethoxybenzoyl, 2,4-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,5-dimethoxybenzoyl, 3,4-dipentyloxybenzoyl, 2-methoxy-4-methoxybenzoyl, 2,4,6-trimethoxybenzoyl, 3,4,5-trimethoxybenzoyl, and the like.

The "phenyl which may optionally have a lower alkoxy substituent" includes a phenyl group which may optionally have one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, and the like.

The "cycloalkyl" includes a cycloalkyl having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.

The "saturated or unsaturated heterocyclic group which is formed by binding the groups R¹¹ and R¹² together with the nitrogen atom to which they bond and may be intervened or not with nitrogen, oxygen or sulfur atom" includes, a 5- to 10-membered, saturated or unsaturated, monocyclic or dicyclic heterocyclic group, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroquinolyl, indolyl, isoindolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1H-indazolyl, 1,2-dihyroquinazolyl, 1,2-dihydrocinnolyl, 1,2-dihydroquinoxalyl, 1,2,3,4-tetrahydroquinazolyl, 1,2,3,4-tetrahydrocinnolyl, 1,2,3,4-tetrahydroquinoxalyl, and the like.

The "phenyl which may optionally have a substituent selected from a lower alkoxy and a lower alkanoyl" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 3-methoxy-4-acetylphenyl, 2-acetylphenyl, 3-acetylphenyl, 4-acetylphenyl, 2-formylphenyl, 3-propionylphenyl, 4-isobutyrylphenyl, 2-pentanoylphenyl, 3-hexanoylphenyl, 3,4-diacetylphenyl, 2,5-diacetylphenyl, 3,4,5-triacetylphenyl, and the like.

The "heterocyclic group which may optionally be substituted by a member selected from benzoyl, a lower alkanoyl, a phenyl(lower)alkyl, and a phenyl having optionally a substituent selected from a lower alkoxy and a lower alkanoyl" includes the above heterocyclic groups which may optionally have a substituent selected from benzoyl group, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenyl group having optionally one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, 3-benzoyl-1-pyrrolidinyl, 4-benzoyl-1-piperidinyl, 4-benzoyl-1-piperazinyl, 4-benzyl-1-piperazinyl, 3-(2-phenylethyl)morpholino, 3-(3-phenylpropyl)thiomorpholino, 3-(4-phenylbutyl)-1-pyrrolyl, 4-acetyl-1-piperidinyl, 4-acetyl-1-piperazinyl, 4-formyl-1-piperazinyl, 2-(5-phenylpentyl)-1-imidazolyl, 3-(6-phenylpentyl)-1-pyrazolyl, 4-(4-methoxyphenyl)-1-piperazinyl, 4-(4-acetylphenyl)-1-piperazinyl, 4-(3-ethoxyphenyl)-1-piperazinyl, 4-(3-propionylphenyl)-1-piperazinyl, 5-benzyl-1,2,3,4-tetrahydroquinolin-1-yl, 6-(4-butyrylphenyl)-1,2,3,4-tetrahydroisoquinolin-2-yl, 4-(2-propoxyphenyl)-1-indolyl, 5-(3-pentanoylphenyl)-1H-indazol-1-yl, 6-(3-butoxyphenyl)-1,2-dihydroquinazolin-1-yl, 7-(4-hexanoylphenyl)-1,2-dihydrocinnolin-2-yl, 6-(4-hexyloxyphenyl)-1,2,3,4-tetrahydroquinoxalin-1-yl, and the like.

The "alkylene" includes a straight chain or branched chain alkylene group having 1 to 12 carbon atoms, for example, in addition to the above-mentioned alkylene groups, heptamethylene, octamethylene, nonamethylene, decamethylene, undecamethylene, dodecamethylene, and the like.

The "lower alkoxycarbonyl(lower)alkyl wherein the alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent" includes a straight chain or branched chain alkoxycarbonylalkyl group having 1 to 6 carbon atoms in the alkoxy moiety, wherein the alkyl moiety is straight chain or branched chain alkyl group having 1 to 6 carbon atoms and has optionaly a substituent selected from a hydroxy group and an amino group having optionally a substituent of a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, 1-hydroxy-1-methoxycarbonylmethyl, 1-methoxycarbonyl-2-hydroxyethyl, 3-hydroxy-3-methoxycarbonylpropyl, 2-hydroxy-4-ethoxycarbonylbutyl, 2-hydroxy-6-propoxycarbonylhexyl, 2-hydroxy-2-pentyloxycarbonylethyl, 1-hydroxy-1-hexyloxycarbonylmethyl, 5-benzyloxycarbonyl-1-methoxycarbonylpentyl, 5-amino-1-methoxycarbonylpentyl, 3-(2-phenylethoxycarbonylamino)-1-ethoxycarbonylpropyl, 4-amino-1-butyloxycarbonylbutyl, and the like.

The "amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from a phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl or a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, or a phenyl(lower)alkoxycarbonyl" includes an amino-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, wherein the alkanoyl moiety may optionally be substituted by a member selected from phenylalkoxycarbonylamino wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, a hydroxy group, a phenyl group having optionally one to three hydroxy-substitutents, a carbamoyl group, an imidazolyl group or a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, and the amino group may optionally have a substituent selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and having optionally one to three hydroxy-substitutents, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, or a phenylalkoxycarbonyl wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, aminoacetyl, 3-formylaminopropionyl, acetylaminoacetyl, 2-propionylaminopropionyl, 4-butyrylaminobutyryl, 2,2-dimethyl-3-isobutyrylaminopropionyl, 5-pentanoylaminopentanoyl, 6-tert-butylcarbonylaminohexanoyl, 3-methyl-4-hexanoylaminobutyryl, 4-methylthio-2-acetylaminobutyryl, 3-(imidazol-4-yl)-2-acetylaminopropionyl, 2-acetylaminopropionyl, 3-(4-hydroxyphenyl)-2-benzyloxycarbonylaminopropionyl, 4-carbomyl-2-acetylaminobutyryl, 2-acetylaminoisopentanoyl, 5-ethylthio-2-acetylaminopentanoyl, 4-(imidazol-2-yl)-2-propionylaminobutyryl, 6-(2-hydroxyphenyl)-2-butyrylaminohexanoyl, 3-carbamoyl-2-benzyloxycarbonylaminopropionyl, 5-carbamoyl-2-(2-phenylethoxycarbonylamino)pentanoyl, 3-(2,4-dihydroxyphenyl)-2-(3-phenylpropoxycarbonylamino)propionyl, 2,5-dibenzyloxycarbonylaminohexanoyl, 3-(4-hydroxyphenyl)-2-aminopropionyl, dimethylaminoacetyl, 3-hydroxy-2-benzyloxycarbonylaminopropionyl, 2-benzyloxycarbonylaminopropionyl, 2-aminopropionyl, 2-aminoisopentanoyl, 2-aminobutyryl, 4-benzyloxycarbonylaminobutyryl, diethylaminoacetyl, 4-acetylaminobutyryl, 4-dimethylaminobutyryl, 2-hdyroxyacetyl, ethylaminoacetyl, allylaminoacetyl, benzylaminoacetyl, isopropylaminoacetyl, (N-methyl-N-benzylamino)acetyl, [N-methyl-N-(2-hydroxyethyl)amino]acetyl, [N-methyl-N-(4-ethoxybenzyl)amino]acetyl, 2-benzyloxycarbonylaminoacetyl, methylsulfonylaminoacetyl, (3-methoxybenzyl)aminoacetyl, (N-methyl-N-acetylamino)acetyl, 5-(N-methyl-N-allylamino)pentanoyl, 6-[N-allyl-N-(3,4-dimethoxybenzyl)amino]hexanoyl, and the like.

The "amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally a hydroxy substituent, imidazolyl, carbamoyl or a lower alkylthio, and the amido group may optionally have a lower alkyl substituent" includes an amido-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms wherein the alkyl moiety have optionally a substituent selected from a phenyl having optionally one to three hydroxy-substituents, an imidazolyl group, a carbamoyl group or a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, and the amido group may optionally have one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,2-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, methylamidomethyl, 1-ethylamidoethyl, 2-propylamidoethyl, 3-isopropylamidopropyl, 4-butylamidobutyl, 5-pentylamidopentyl, 6-hexylamidohexyl, dimethylamidomethyl, (N-ethyl-N-propylamido)methyl, 2-(N-methyl-N-hexylamido)ethyl, 2-(4-hydroxyphenyl)carbamoylethyl, 1-carbamoylisobutyl, 2-(imidazol-4-yl)-1-carbamoylethyl, 1,3-dicarbamoylpropyl, 3-methylthio-1-carbamoylpropyl, 3-(2-hydroxyphenyl)-1-methylamidopropyl, 4-(2,6-dihydroxyphenyl)-1-(N-methyl-N-hexylamido)butyl, 3-(imidazol-2-yl)-1-propylamidopropyl, 1,4-dicarbamoylbutyl, 2-ethylthio-1-butylamidobutyl, 4-pentylthio-1-hexylamidobutyl, and the like.

The "carboxy(lower)alkyl" includes a carboxyalkyl group wherein the alkyl moietyl is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.

The "lower alkoxy(lower)alkyl" includes a straight chain or branched chain alkoxyalkyl group having 1 to 6 carbon atoms in the alkoxy moiety wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methoxymethyl, 2-ethoxyethyl, 1-methoxyethyl, 3-methoxypropyl, 4-ethoxybutyl, 6-propoxyhexyl, 5-isopropoxypentyl, 1,1-dimethyl-2-butoxyethyl, 2-methyl-3-tert-butoxypropyl, 2-pentyloxyethyl, hexyloxymethyl, and the like.

The "amino acid residue which is able to form an amido bond with the amino group to which R⁴ and R⁵ bind" includes, for example, alanine residue, N² -arginine residue, N⁵ -arginine residue, N⁶ -arginine residue, N⁴ -asparagine residue, aspattic acid residue, N⁵ -glutamine residue, cysteine residue, glutamic acid residue, glycine residue, histidine residue, isoleucine residue, leucine residue, N² -lysine residue, N⁶ -lysine residue, methionine residue, phenylalanine residue, proline residue, serine residue, threonine residue, tryptophane residue, tyrosine residue, valine residue, and the like.

The "hydroxyimino-substituted lower alkyl" includes a hydroxyimino-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, hydroxyiminomethyl, 1-hydroxyiminoethyl, 2-hydroxyiminoethyl, 3-hydroxyiminopropyl, 4-hydroxyiminobutyl, 5-hydroxyiminopentyl, 6-hydroxyiminohexyl, 1,1-dimethyl-2-hydroxyiminoethyl, 2-methyl-3-hydroxyiminopropyl, and the like.

The "halogen-substituted lower alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by one. to three halogen atoms, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.

The "phenyl(lower)alkoxycarbonyl" includes a phenylalkoxycarbonyl wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.

The "lower alkoxy(lower)alkoxy which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a lower alkyl" includes an alkoxy-alkoxy group wherein both alkoxy moiety are each a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by one or two substituents selected from hydroxy and an amino being optionally substituted by a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, hydroxymethoxymethoxy, 3-(2-hydroxyethoxy)propoxy, 4-(1-hydroxyethoxy)butoxy, 6-(3-hydroxypropoxy)hexyloxy, 5-(2,3-dihydroxypropoxy)pentyloxy, 1,1-dimethyl-2-(4-hydroxybutoxy)ethoxy, 2-methyl-3-(3,4-dihydroxybutoxy)propoxy, 2-(1,1-dimethyl-2-hydroxyethoxy)ethoxy, (5-hydroxypentyloxy)methoxy, (6-hydroxyhexyloxy)methoxy, (2-methyl-3-hydroxypropoxy)methoxy, aminomethoxymethoxy, 2-(1-aminoethoxy)ethoxy, 1-(2-aminoethoxy)ethoxy, 3-(3-aminopropoxy)propoxy, 4-(4-aminobutoxy)butoxy, 5-(5-aminopentyloxy)pentyloxy, 6-(6-aminohexyloxy)hexyloxy, (1,1-dimethyl-2-aminoethoxy)methoxy, (2-methyl-3-aminopropoxy)methoxy, 1,1-dimethyl-2-(methylaminomethoxy)ethoxy, 2-methyl-3-(ethylaminomethoxy)propoxy, propylaminomethoxymethoxy, 1-(isopropylaminomethoxy)ethoxy, 2-(butylaminomethoxy)ethoxy, 3-(tert-butylaminomethoxy)propoxy, 4-(pentylaminomethoxy)butoxy, 5-(hexylaminomethoxy)pentyloxy, 6-(dimethylaminomethoxy)hexyloxy, 1,1-dimethyl-2-(diethylaminomethoxy)ethoxy, 2-methyl-3-(dipropylaminomethoxy)propoxy, dibutylaminomethoxymethoxy, 1-(dipentylaminomethoxy)ethoxy, 2-(dihexylaminomethoxy)ethoxy, 3-(N-methyl-N-ethylaminomethoxy)propoxy, 4-(N-methyl-N-propylaminomethoxy)butoxy, 5-(N-methyl-N-butylaminomethoxy)pentyloxy, 6-(N-methyl-N-hexylaminomethoxy)hexyloxy, (1-methylaminoethoxy)methoxy, 1-(2-ethylaminoethoxy)ethoxy, 2-(3-propylaminopropoxy)ethoxy, 3-(4-butylaminobutoxy)propoxy, 4-(1,1-dimethyl-2-pentylaminoethoxy)butoxy, 5-(5-hexylaminopentyloxy)pentyloxy, 6-(6-dimethylaminohexyloxy)hexyloxy, 3-(2-diethylaminoethoxy)propoxy, 4-[1-(N-methyl-N-hexylamino)ethoxy]butoxy, 5-(3-dihexylaminopropoxy)pentyloxy, 6-(4-dibutylaminobutoxy)hexyloxy, 3-[2-(N-methyl-N-pentylamino)ethoxy]propoxy, 5-(2-hydroxy-3-dimethylaminopropoxy)pentyloxy, 5-(2-hydroxy-3-diethylaminopropoxy)pentyloxy, 3-(2-hydroxy-3-diethylaminopropoxy)propoxy, 4-(3-hydroxy-4-methylaminobutoxy)butoxy, 5-(4-hydroxy-5-dimethylaminopentyloxy)pentyloxy, 6-(4-hydroxy-5-methylaminopentyloxy)hexyloxy, and the like.

The "morpholinyl-substituted lower alkoxy which may optionally have a substituent selected from a lower alkyl and oxo" includes a morpholinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and an oxo group, for example, (2-morpholinyl)methoxy, 2-(3-morpholinyl)ethoxy, 1-(3-morpholinyl)ethoxy, 3-(2-morpholinyl)propoxy, 4-(3-morpholinyl)butoxy, 5-(2-morpholinyl)pentyloxy, 6-(3-morpholinyl)hexyloxy, 1,1-dimethyl-2-(3-morpholinyl)ethoxy, 2-methyl-3-(2-morpholinyl)propoxy, 6-(1-methyl-5-oxo-3-morpholinyl)hexyloxy, (1-ethyl-2-morpholinyl)methoxy, 2-(2-oxo-3-morpholinyl)ethoxy, 1-(2-propyl-3-morpholinyl)ethoxy, 3-(3-butyl-2-morpholinyl)propoxy, 4-(5-pentyl-3-morpholinyl)butoxy, 5-(6-hexyl-2-morpholinyl)pentyloxy, 3-(5-oxo-1-propyl-2-morpholinyl)propoxy, 4-(2-oxo-1-butyl-3-morpholinyl)butoxy, 5-(3-oxo-1-pentyl-6-morpholinyl)pentyloxy, 6-(2-oxo-1-hexyl-5-morpholinyl)hexyloxy, and the like.

The "benzimidazolylthio-substituted lower alkoxy" includes a benzimidazolylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (benzimidazol-2-yl)thiomethoxy, 1-(benzimidazol-4-yl)thioethoxy, 2-(benzimidazol-5-yl)thioethoxy, 3-(benzimidazol-6-yl)thiopropoxy, 4-(benzimidazol-2-yl)thiobutoxy, 5-(benzimidazol-7-yl)thiopentyloxy, 6-(benzimidazol-2-yl)thiohexyloxy, 1,1-dimethyl-2-(benzimidazol-2-yl)thioethoxy, 2-methyl-3-(benzimidazol-2-yl)thiopropoxy, and the like.

The "benzimidazolylsulfinyl-substituted lower alkoxy" includes a benzimidazolylsulfinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (benzimidazol-2-yl)sulfinylmethoxy, 1-(benzimidazol-4-yl)sulfinylethoxy, 3-(benzimidazol-6-yl)sulfinylpropoxy, 4-(benzimidazol-2-yl)sulfinylbutoxy, 5-(benzimidazol-7-yl)sulfinylpentyloxy, 6-(benzimidazol-2-yl)sulfinylhexyloxy, 1,1-dimethyl-2-(benzimidazol-2-yl)sulfinylethoxy, 2-methyl-3-(benzimidazol-2-yl)sulfinylpropoxy, and the like.

The "tetrahydropyranyl-substituted lower alkyl" includes a tetrahydropyranyl-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-, 3- or 4-tetrahydropyranyl)methyl, 2-(2-, 3- or 4-tetrahydropyranyl)ethyl, 1-(2-, 3- or 4-tetrahydropyranyl)ethyl, 3-(2-, 3- or 4-tetrahydropyranyl)propyl, 4-(2-, 3- or 4-tetrahydropyranyl)butyl, 5-(2-, 3- or 4-tetrahydropyranyl)pentyl, 6-(2-, 3- or 4-tetrahydropyranyl)hexyl, 1,1-dimethyl-2-(2-, 3- or 4-tetrahydropyranyl)ethyl, 2-methyl-3-(2-, 3- or 4-tetrahydropyranyl)propyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed by binding R³² and R³³ together with the nitrogen atom to which they bond with being intervened or not with nitrogen, oxygen or sulfur atom" includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and the like.

The "heterocyclic group having a substituent selected from carbamoyl, a lower alkyl, a phenyl(lower)alkyl, phenyl and a hydroxy-substituted lower alkyl" includes the above-mentioned heterocyclic groups which have one to three substituents selected from a carbamoyl group, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group and a hydroxy-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 4-phenylpiperazinyl, 2-phenylpyrrolidinyl, 4-phenylpiperidinyl, 3-phenylmorpholino, 3-phenylthiomorpholino, 4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(3-phenylpropyl)pyrrolidinyl, 4-(4-phenylbutyl)piperidinyl, 3-(5-phenylpentyl)morpholino, 2-(6-phenylhexyl)thiomorpholino, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 2-hexylthiomorpholino, 4-ethylpiperazinyl, 3-methyl-4-phenylpiperazinyl, 3-ethyl-4-benzylpiperidinyl, 3-methyl-4-benzylpyrrolidinyl, 3-methyl-5-phenylmorpholino, 3-methyl-5-(2-hydroxyethyl)thiomorpholino, 4-(2-hydroxyethyl)piperazinyl, 2-(hydroxymethyl)pyrrolidinyl, 4-(4-hydroxybutyl)piperidinyl, 2-(5-hydroxypentyl)thiomorpholino, 3-(6-hydroxyhexyl)morpholino, 2-methyl-4-(2-hydroxyethyl)pyrrolidinyl, 2-carbamoylpyrrolidinyl, 3-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl, 3-carbamoylpiperazinyl, 2-carbamoylpiperazinyl, 4-carbamoylpiperidinyl, 3-carbamoylpiperidinyl, 2-2ylpiperidinyl, 3-carbamoylmorpholino, 2-carbamoylthiomorpholino, 2-methyl-3-carbamoylpyrrolidinyl, 3-methyl-4-carbamoylpiperidinyl, 2,6-dimethyl-4-carbamoylpiperazinyl, and the like.

The "amino having optionally a phenyl(lower)alkoxycarbonyl substituent" includes an amino group which may optionally have a substituent of a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, amino, benzyloxycarbonylamino, (2-phenylethoxycarbonyl)amino, (1-phenylethoxycarbonyl)amino, (3-phenylpropoxycarbonyl)amino, (4-phenylbutoxycarbonyl)amino, (5-phenylpentyloxycarbonyl)amino, (6-phenylhexyloxycarbonyl)amino, (1,1-dimethyl-2-phenylethoxycarbonyl)amino, (2-methyl-3-phenylpropoxycarbonyl)amino, and the like.

The "phenyl having optionally hydroxy substituent" includes a phenyl group having optionally one to three hydroxy-substituents, for example, phenyl, 4-hydroxyphenyl, 3-hydroxyphenyl, 2-hydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 2,3,4-trihydroxyphenyl, and the like.

The "phenylsulfonyl which phenyl ring may optionally have a substituent selected from a lower alkyl, nitro, and an amino having optionally one or two substituents selected from a lower alkanoyl and lower alkyl" includes a phenylsulfonyl group which phenyl ring may optionally have one to three substitutents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a nitro group, an amino group having optionally one or two substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, phenylsulfonyl, 2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 2-ethylphenylsulfonyl, 3-ethylphenylsulfonyl, 4-ethylphenylsulfonyl, 4-isopropylphenylsulfonyl, 4-butylphenylsulfonyl, 2-pentylphenylsulfonyl, 3-hexylphenylsulfonyl, 2,4-dimethylphenylsulfonyl, 3,4-diethylphenylsulfonyl, 3,4,5-trimethylphenylsulfonyl, 4-aminophenylsulfonyl, 3-aminophenylsulfonyl, 2-aminophenylsulfonyl, 3,4-diaminophenylsulfonyl, 2,5-diaminophenylsulfonyl, 2,4,6-triaminophenylsulfonyl, 4-nitrophenylsulfonyl, 3-nitrophenylsulfonyl, 2-nitrophenylsulfonyl, 2,3-dinitrophenylsulfonyl, 2,6-dinitrophenylsulfonyl, 2,4,6-trinitrophenylsulfonyl, 4-acetylaminophenylsulfonyl, 4-dimethylaminophenylsulfonyl, 3-(N-methyl-N-acetylamino)phenylsulfonyl, 2-methyl-4-aminophenylsulfonyl, 3-nitro-4-methylphenylsulfonyl, 2-ethylaminophenylsulfonyl, 2-methyl-3-diethylaminophenylsulfonyl, and the like.

The "amino-substituted lower alkyl which may optionally have a substituent selected from a lower alkyl and a lower alkanoyl" include a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, 2-(acetylamino)ethyl, 3-(acetylamino)propyl, formylaminomethyl, 1-(propionylamino)ethyl, 4-(butyrylamino)butyl, 5-(pentanoylamino)pentyl, 5-(hexanoylamino)hexyl, 2-(N-methyl-N-acetylamino)ethyl, 1-(N-ethyl-N-acetylamino)ethyl, and the like.

The "piperidinyl having optionally a phenyl(lower)alkyl substituent" includes a piperidinyl which has optionally a substituent of a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 4-piperidinyl, 3-piperidinyl, 2-piperidinyl, 1-benzyl-4-piperidinyl, 1-(2-phenylethyl)-3-piperidinyl, 2-(3-phenylpropyl)-5-piperidinyl, 3-(4-phenylbutyl)-6-piperidinyl, 4-(5-phenylpentyl)-3-piperidinyl, 5-(6-phenylhexyl)-4-piperidinyl, 2-benzyl-4-piperidinyl, 1-(3-phenylpropyl)-4-piperidinyl, and the like.

The "imidazo[4,5-c]pyridylcarbonyl(lower)alkoxy" includes an imidazo[4,5-c]pyridylcarbonylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (imidazo[4,5-c]pyridin-2-yl)carbonylmethoxy, 2-(imidazo[4,5-c]pyridin-2-yl)carbonylethoxy, 1-(imidazo[4,5-c]pyridin-4-yl)carbonylethoxy, 3-(imidazo[4,5-c]pyridin-5-yl)carbonylpropoxy, 4-(imidazo[4,5-c]pyridin-7-yl)carbonylbutoxy, 5-(imidazo[4,5-c]pyridin-2-yl)carbonylpentyloxy, 6-(imidazo[4,5-c]pyridin-2-yl)carbonylhexyloxy, 1,1-dimethyl-2-(imidazo[4,5-c]pyridin-2-yl)carbonylethoxy, 2-methyl-3-(imidazo[4,5-c]pyridin-2-yl)carbonylpropoxy, and the like.

The "tri(lower alkyl)ammonium" includes an ammonium group having three of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, trimethylammonium, triethylammonium, tripropylammonium, triisopropylammonium, tributylammonium, tri(tert-butyl)ammonium, tripentylammonium, trihexylammonium, dimethylethylammonium, diethylpropylammonium, dimethylbutylammonium, diethylmethylammonium, dimethylhexylammonium, dipropylmethylammonium, dibutylethylammonium, methylethylpropylammonium, methylbutylpentylammonium, and the like.

The "pyridyl(lower)alkyl" include a pyridylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-pyridyl)methyl, (3-pyridyl)methyl, (4-pyridyl)methyl, 2-(2-pyridyl)ethyl, 1-(3-pyridyl)ethyl, 3-(4-pyridyl)propyl, 4-(2-pyridyl)butyl, 5-(3-pyridyl)pentyl, 6-(4-pyridyl)hexyl, 1,1-dimethyl-2-(2-pyridyl)ethyl, 2-methyl-3-(3-pyridyl)propyl, and the like.

The "lower alkyl which may optionally have a substituent selected from hydroxy and cyano" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have one to three substituents selected from a hydroxy group and a cyano group, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, 2,3-dihydroxyethyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.

The "lower alkynyl" includes a straight chain or branched chain alkynyl group having 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, and the like.

The "pyrrolidinylcarbonyl which may optionally be substituted by a phenyl(lower)alkoxycarbonyl on the pyrrolidine group" includes a pyrrolidinylcarbonyl which may optionally be substituted by a phenylalkoxycarbonyl group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, 1-benzyloxycarbonyl-2-pyrrolidinylcarbonyl, 2-pyrrolidinylcarbonyl, 1-pyrrolidinylcarbonyl, 3-pyrrolidinylcarbonyl, 1-(2-phenylethoxycarbonyl)-2-pyrrolidinylcarbonyl, 2-(1-phenylethoxycarbonyl)-1-pyrrolidinylcarbonyl, 3-(3-phenylpropoxycarbonyl)-2-pyrrolidinylcarbonyl, 1-(4-phenylbutoxycarbonyl)-2-pyrrolidinylcarbonyl, 2-(5-phenylpentyloxycarbonyl)-1-pyrrolidinylcarbonyl, 2-(6-phenylhexyloxycarbonyl)-3-pyrrolidinylcarbonyl, and the like.

The "phenyl(lower)alkoxycarbonylamino" includes a phenylalkoxycarbonylamino wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms, for example, N-benzyloxycarbonylamino, N-(2-phenylethoxycarbonyl)amino, N-(1-phenylethoxycarbonyl)amino, N-(3-phenylpropoxycarbonyl)amino, N-(4-phenylbutoxycarbonyl)amino, N-(5-phenylpentyloxycarbonyl)amino, N-(6-phenylhexyloxycarbonyl)amino, N-(1,1-dimethyl-2-phenylethoxycarbonyl)amino, N-(2-methyl-3-phenylpropoxycarbonyl)amino, and the like.

The "lower alkyl having optionally a hydroxy-substituent" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which has optionally one to three hydroxy-substituents, for example, in addition to the above-mentioned lower alkyl groups, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, 3,4-dihydroxybutyl, 5,6-dihydroxyhexyl, and the like.

The "hydroxy-substituted lower alkanoyl" includes a hydroxy-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4-hydroxybutyryl, 2,2-dimethyl-3-hydroxypropionyl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 3-methyl-4-hydroxybutyryl, and the like.

The "lower alkanoyloxy(lower)alkanoyl" includes an alkanoyloxyalkanoyl wherein both alkanoyl moieties are a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-propionyloxypropionyl, 2-butyryloxypropionyl, 4-pentanoyloxybutyryl, 2,2-dimethyl-3-hexanoyloxypropionyl, 5-acetyloxypentanoyl, 6-propionyloxyhexanoyl, and the like.

The "phenyl(lower)alkyl which phenyl ring may optionally have a lower alkoxy substituent" includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and the phenyl ring has optionally one to three substituents of a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, in addition to the above-mentioned phenyl(lower)alkyl groups, 2-methoxybenzyl, 3-methoxybenzyl, 2-(4-methoxyphenyl)ethyl, 1-(2-ethoxyphenyl)ethyl, 3-(4-isopropoxyphenyl)propyl, 4-(3-pentyloxyphenyl)butyl, 5-(4-hexyloxyphenyl)pentyl, 6-(2-butyloxyphenyl)hexyl, 3,4-dimethoxybenzyl, 3-ethoxy-4-methoxybenzyl, 2,3-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, and the like.

The "cycloalkenylcarbonyl" includes a cycloalkenylcarbonyl group having 3 to 8 carbon atoms, for example, cyclopropenylcarbonyl, cyclobutenylcarbonyl, cyclopentenylcarbonyl, cyclohexenylcarbonyl, cycloheptenylcarbonyl, cyclooctenylcarbonyl, and the like.

The "pyrimidylthio-substituted lower alkoxy" includes a pyrimidylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)thiomethoxy, 2-(4-pyrimidyl)thioethoxy, 1-(5-pyrimidyl)thioethoxy, 3-(6-pyrimidyl)thiopropoxy, 4-(4-pyrimidyl)thiobutoxy, 5-(2-pyrimidyl)thiopentyloxy, 6-(5-pyrimidyl)thiohexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)thioethoxy, 2-methyl-3-(2-pyrimidyl)thiopropoxy, and the like.

The "pyrimidylsulfinyl-substituted lower alkoxy" includes a pyrimidylsulfinyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)sulfinylmethoxy, 2-(4-pyrimidyl)sulfinylethoxy, 1-(5-pyrimidyl)sulfinylethoxy, 3-(6-pyrimidyl)sulfinylpropoxy, 4-(4-pyrimidyl)sulfinylbutoxy, 5-(2-pyrimidyl)sulfinylpentyloxy, 6-(5-pyrimidyl)sulfinylhexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)sulfinylethoxy, 2-methyl-3-(2-pyrimidyl)sulfinylpropoxy, and the like.

The "pyrimidylsulfonyl-substituted lower alkoxy" includes a pyrimidylsulfonyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrimidyl)sulfonylmethoxy, 2-(4-pyrimidyl)sulfonylethoxy, 1-(5-pyrimidyl)sulfonylethoxy, 3-(6-pyrimidyl)sulfonylpropoxy, 4-(4-pyrimidyl)sulfonylbutoxy, 5-(2-pyrimidyl)sulfonylpentyloxy, 6-(5-pyrimidyl)sulfonylhexyloxy, 1,1-dimethyl-2-(2-pyrimidyl)sulfonylethoxy, 2-methyl-3-(2-pyrimidyl)sulfonylpropoxy, and the like.

The "imidazolylthio-substituted lower alkoxy which may optionally have a lower alkyl substituent" includes a imidazolylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have a substituent of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the imidazolyl group, for example, (2-imidazolyl)thiomethoxy, 2-(4-imidazolyl)thioethoxy, 1-(5-imidazolyl)thioethoxy, 3-(2-imidazolyl)thiopropoxy, 4-(4-imidazolyl)thiobutoxy, 5-(2-imidazolyl)thiopentyloxy, 6-(5-imidazolyl)thiohexyloxy, 1,1-dimethyl-2-(2-imidazolyl)thioethoxy, 2-methyl-3-(2-imidazolyl)thiopropoxy, (4-methyl-2-imidazolyl)thiomethoxy, 2-(5-ethyl-4-imidazolyl)thioethoxy, 1-(4-propyl-5-imidazolyl)thioethoxy, 3-(1-butyl-2-imidazolyl)thiopropoxy, 4-(2-pentyl-4-imidazolyl)thiobutoxy, 5-(1-methyl-2-imidazolyl)thiopentyloxy, 6-(1-hexyl-5-imidazolyl)thiohexyloxy, 1,1-dimethyl-2-(1-ethyl-2-imidazolyl)thioethoxy, 2-methyl-3-(1-propyl-2-imidazolyl)thiopropoxy, and the like.

The "imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent" includes a imidazolylsulfonyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have a substituent of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms on the imidazolyl group, for example, (2-imidazolyl)sulfonylmethoxy, 2-(4-imidazolyl)sulfonylethoxy, 1-(5-imidazolyl)sulfonylethoxy, 3-(2-imidazolyl)sulfonylpropoxy, 4-(4-imidazolyl)sulfonylbutoxy, 5-(2-imidazolyl)sulfonylpentyloxy, 6-(5-imidazolyl)sulfonylhexyloxy, 1,1-dimethyl-2-(2-imidazolyl)sulfonylethoxy, 2-methyl-3-(2-imidazolyl)sulfonylpropoxy, (4-methyl-2-imidazolyl)sulfonylmethoxy, 2-(5-ethyl-4-imidazolyl)sulfonylethoxy, 1-(4-propyl-5-imidazolyl)sulfonylethoxy, 3-(1-butyl-2-imidazolyl)sulfonylpropoxy, 4-(2-pentyl-4-imidazolyl)sulfonylbutoxy, 5-(1-methyl-2-imidazolyl)sulfonylpentyloxy, 6-(1-hexyl-5-imidazolyl)sulfonylhexyloxy, 1,1-dimethyl-2-(1-ethyl-2-imidazolyl)sulfonylethoxy, 2-methyl-3-(1-propyl-2-imidazolyl)sulfonylpropoxy, and the like.

The "ammonium-substituted lower alkoxy having three substituents selected from a lower alkyl, a lower alkenyl and oxo" includes an ammonium-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which have three substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, and an oxo group, for example, trimethylammoniummethoxy, 2-(triethylammonium)ethoxy, 1-(tripropylammonium)ethoxy, 3-(tributylammonium)propoxy, 4-(tripentylammonium)butoxy, 5-(triethylammonium)pentyloxy, 6-(trihexylammonium)hexyloxy, 1,1-dimethyl-2-(triallylammonium)ethoxy, 2-methyl-3-(tributenylammonium)propoxy, tri(1-methylallyl)ammonium-methoxy, 2-[tri(2-pentenyl)ammonium]ethoxy, 1-[tri(2-hexenyl)ammonium]ethoxy, 3-(N-allyl-N,N-dimethylammonium)propoxy, 4-(N,N-diallyl-N-methylammonium)butoxy, 5-(N-allyl-N-methylamino)pentyloxy N-oxide, 6-(N-allyl-N-ethylamino)hexyloxy N-oxide, 5-(N-allyl-N-methyl-N-ethylammonium)pentyloxy, and the like.

The "phenylthio(lower)alkoxy which phenyl ring may optionally have a substituent selected from nitro and an amino" includes a phenylthioalkoxy wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and the phenyl ring may optionally have one to three substituents selected from a nitro group and an amino group, for example, phenylthiomethoxy, 2-phenylthioethoxy, 1-phenylthioethoxy, 3-phenylthiopropoxy, 4-phenylthiobutoxy, 5-phenylthiopentyloxy, 6-phenylthiohexyloxy, 1,1-dimethyl-2-phenylthioethoxy, 2-methyl-3-phenylthiopropoxy, (2-nitrophenyl)thiomethoxy, 2-(3-nitrophenyl)thioethoxy, 1-(4-nitrophenyl)thioethoxy, 3-(2,3-dinitrophenyl)thiopropoxy, 4-(3,4-dinitrophenyl)thiobutoxy, 5-(4-nitrophenyl)thiopentyloxy, 6-(2,6-dinitrophenyl)thiohexyloxy, 1,1-dimethyl-2-(2,4,6-trinitrophenyl)thioethoxy, 2-methyl-3-(4-nitrophenyl)thiopropoxy, (2-aminophenyl)thiomethoxy, 2-(3-aminophenyl)thioethoxy, 1-(4-aminophenyl)thioethoxy, 3-(2,3-diaminophenyl)thiopropoxy, 4-(3,4-diaminophenyl)thiobutoxy, 5-(4-aminophenyl)thiopentyloxy, 6-(2,6-diaminophenyl)thiohexyloxy, 1,1-dimethyl-2-(2,4,6-triaminophenyl)thioethoxy, 2-methyl-3-(4-aminophenyl)thiopropoxy, and the like.

The "phenylsulfonyl(lower)alkoxy which phenyl ring may optionally have a substituent selected from nitro and an amino having optionally one or two substituents selected from a lower alkanoyl and a lower alkyl" includes a phenylsulfonylalkoxy wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, and the phenyl ring may optionally have one to three substituents selected from a nitro group and an amino group having optionally one or two substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, phenylsulfonylmethoxy, 2-phenylsulfonylethoxy, 1-phenylsulfonylethoxy, 3-phenylsulfonylpropoxy, 4-phenylsulfonylbutoxy, 5-phenylsulfonylpentyloxy, 6-phenylsulfonylhexyloxy, 1,1-dimethyl-2-phenylsulfonylethoxy, 2-methyl-3-phenylsulfonylpropoxy, (2-aminophenyl)sulfonylmethoxy, 5-(4-aminophenyl)sulfonylpentyloxy, 2-(4-methylaminophenyl)sulfonylethoxy, 1-(3-ethylaminophenyl)sulfonylethoxy, 3-[2-(N-methyl-N-ethylamino)phenyl]sulfonylpropoxy, 4-[3-(N-methyl-N-hexylamino)phenyl]sulfonylbutoxy, 5-(4-dimethylaminophenyl)sulfonylpentyloxy, 4-dipentylaminophenylsulfonylmethoxy, 2-(2-isopropylaminophenyl)sulfonylethoxy, 1-(3-butylaminophenyl)sulfonylethoxy, 5-(2,4-diaminophenyl)sulfonylpentyloxy, 3-[2,3-bis(dimethylamino)phenyl]sulfonylpropoxy, 4-[3,4-bis(methylamino)phenyl]sulfonylbutoxy, 5-(2,4,6-triaminophenyl)sulfonylpentyloxy, 6-[3,4,5-tri(methylamino)phenyl]sulfonylhexyloxy, 5-(4-acetylaminophenyl)sulfonylpentyloxy, 3-[4-(N-methyl-N-acetylamino)phenyl]sulfonylpropoxy, 5-(4-nitrophenyl)sulfonylpentyloxy, 2-(4-nitro-3-methylaminophenyl)sulfonylethoxy, 3-(2,4-dinitrophenyl)sulfonylpropoxy, 4-(2,4,6-trinitrophenyl)sulfonylbutoxy, and the like.

The "pyridylthio-substituted lower alkoxy" includes a pyridylthio-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyridyl)thiomethoxy, 2-(3-pyridyl)thioethoxy, 1-(4-pyridyl)thioethoxy, 3-(3-pyridyl)thiopropoxy, 4-(4-pyridyl)thiobutoxy, 5-(2-pyridyl)thiopentyloxy, 5-(4-pyridyl)thiopentyloxy, 6-(3-pyridyl)thiohexyloxy, 1,1-dimethyl-2-(2-pyridyl)thioethoxy, 2-methyl-3-(4-pyridyl)thiopropoxy, and the like.

The "pyridylsulfonyl-substituted lower alkoxy which may optionally have an oxo subsituent on the pyridyl ring" includes a pyridylsulfonyl-substituted straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which may optionally have an oxo substituent on the pyridyl ring, for example, (2-pyridyl)sulfonylmethoxy, 2-(3-pyridyl)sulfonylethoxy, 1-(4-pyridyl)sulfonylethoxy, 3-(3-pyridyl)sulfonylpropoxy, 4-(4-pyridyl)sulfonylbutoxy, 5-(2-pyridyl)sulfonylpentyloxy, 5-(4-pyridyl)sulfonylpentyloxy, 6-(3-pyridyl)sulfonylhexyloxy, 1,1-dimethyl-2-(2-pyridyl)sulfonylethoxy, 2-methyl-3-(4-pyridyl)sulfonylpropoxy, 5-(1-oxido-4-pyridyl)sulfonylpentyloxy, (4-oxo-2-pyridyl)sulfonylmethoxy, 2-(1-oxido-3-pyridyl)sulfonylethoxy, 1-(2-oxo-4-pyridyl)sulfonylethoxy, 3-(2-oxo-3-pyridyl)sulfonylpropoxy, 4-(3-oxo-4-pyridyl)sulfonylbutoxy, 5-(1-oxido-2-pyridyl)sulfonylpentyloxy, 6-(1-oxido-3-pyridyl)sulfonylhexyloxy, and the like.

The "cycloalkylcarbonyl having optionally one to three substituents selected from hydroxy and a lower alkanoyloxy" includes a cycloalkylcarbonyl having 3 to 8 carbon atoms which has optionally one to three substituents selected from a hydroxy group and a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, 2-hydroxycyclopropylcarbonyl, 3-hydroxycyclobutylcarbonyl, 2-hydroxycyclopentylcarbonyl, 3-hydroxycyclopentylcarbonyl, 2,4-dihydroxycyclopentylcarbonyl, 2-hydroxycyclohexylcarbonyl, 3-hydroxycyclohexylcarbonyl, 4-hydroxycyclohexylcarbonyl, 3,4-dihydroxycyclohexylcarbonyl, 2,4-dihydroxycyclohexylcarbonyl, 2,5-dihydroxycyclohexylcarbonyl, 3,4,5-trihydroxycyclohexylcarbonyl, 3-hydroxycycloheptylcarbonyl, 3,4-dihydroxycycloheptylcarbonyl, 2,3,4-trihydroxycycloheptylcarbonyl, 4-hydroxycyclooctylcarbonyl, 4,5-dihydroxycyclooctylcarbonyl, 4,5,6-trihydroxycyclooctylcarbonyl, 2-acetyloxycyclopropylcarbonyl, 3-propionyloxycyclobutylcarbonyl, 2-butyryloxycyclopentylcarbonyl, 3-pentanoyloxycyclopentylcarbonyl, 2,4-dihexanoyloxycyclopentylcarbonyl, 2-acetyloxycyclohexylcarbonyl, 3-propionyloxycyclohexylcarbonyl, 4-butyryloxycyclohexylcarbonyl, 3,4-diacetyloxycyclohexylcarbonyl, 2,4-diacetyloxycyclohexylcarbonyl, 2,5-diacetyloxycyclohexylcarbonyl, 3,4,5-triacetyloxycyclohexylcarbonyl, 3,4-diacetyloxy-5-hyroxycyclohexylcarbonyl, 3-pentanoyloxycycloheptylcarbonyl, 3,4-diacetyloxycycloheptylcarbonyl, 2,3,4-tripropionyloxycycloheptylcarbonyl, 4-hexanoyloxycyclooctylcarbonyl, 4,5-dibutyryloxycyclooctylcarbonyl, 4,5,6-triacetyloxycyclooctylcarbonyl, and the like.

The "tetrahydroypyranyl(lower)alkyl which tetrahydroxypyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy" includes a tetrahydropyranylalkyl wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and the tetrahydropyranyl ring may optionally have one to four substituents selected from a hydroxy group and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-tetrahydropyranyl)methyl, 2-(3-tetrahydropyranyl)ethyl, 1-(4-tetrahydropyranyl)ethyl, 3-(2-tetrahydropyranyl)propyl, 4-(3-tetrahydropyranyl)butyl, 5-(4-tetrahydropyranyl)pentyl, 6-(2-tetrahydropyranyl)hexyl, 1,1-dimethyl-2-(3-tetrahydropyranyl)ethyl, 2-methyl-3-(4-tetrahydropyranyl)propyl, (3-hydroxy-2-tetrahydropyranyl)methyl, 2-(2,4-dihydroxy-3-tetrahydropyranyl)ethyl, 1-(2,3,5-trihydroxy-4-tetrahydropyranyl)ethyl, 3-(6-methoxy-2-tetrahydropyranyl)propyl, 4-(4-ethoxy-3-tetrahydropyranyl)butyl, 5-(4,6-dimethoxy-4-tetrahydropyranyl)pentyl, 6-(4,5,6-trimethoxy-2-tetrahydropyranyl)hexyl, 1,1-dimethyl-2-(2-propoxy-3-tetrahydropyranyl)ethyl, 2-methyl-3-(6-butoxy-4-tetrahydropyranyl)propyl, (6-pentyloxy-2-tetrahydropyranyl)methyl, 2-(4-hexyloxy-3-tetrahydropyranyl)ethyl, 2-(3,4,5-trihydroxy-6-methoxy-2-tetrahydropyranyl)methyl, 1-(3,4,5,6-tetrahydroxy-2-tetrahydropyranyl)ethyl, 3-(3,4,5,6-tetramethoxy-2-tetrahydropyranyl)propyl, and the like.

The "lower alkanoyl substituted by a 5- or 6-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl" includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by a 5- or 6-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl, and morpholinyl, for example, 2-(1-pyrrolidinyl)acetyl, 3-(2-pyrrolidinyl)propionyl, 2-(3-pyrrolidinyl)propionyl, 4-(1-pyrrolidinyl)butyryl, 2,2-dimethyl-3-(2-pyrrolidinyl)propionyl, 5-(3-pyrrolidinyl)pentanoyl, 6-(1-pyrrolidinyl)hexanoyl, 2-(1-piperazinyl)acetyl, 3-(2-piperazinyl)propionyl, 2-(3-piperazinyl)propionyl, 4-(1-piperazinyl)butyryl, 2,2-dimethyl-3-(2-piperazinyl)propionyl, 5-(3-piperazinyl)pentanoyl, 6-(1-piperazinyl)hexanoyl, 2-(1-piperidinyl)acetyl, 3-(2-piperidinyl)propionyl, 2-(3-piperidinyl)propionyl, 4-(4-piperidinyl)butyryl, 2,2-dimethyl-3-(1-piperidinyl)propionyl, 5-(2-piperidinyl)pentanoyl, 6-(3-piperidinyl)hexanoyl, 2-(1-morpholinyl)acetyl, 3-(2-morpholinyl)propionyl, 2-(3-morpholinyl)propionyl, 4-(1-morpholinyl)butyryl, 2,2-dimethyl-3-(2-morpholinyl)propionyl, 5-(3-morpholinyl)pentanoyl, 6-(1-morpholinyl)hexanoyl, and the like.

The above "heterocyclic group-substituted lower alkanoyl which has a substituent selected from a lower alkyl and phenyl" includes the above heterocyclic group-substituted straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which has one to three substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a phenyl group, for example, 2-(2-methyl-1-pyrrolidinyl)acetyl, 3-(1-ethyl-2-pyrrolidinyl)propionyl, 2-(1-propyl-3-pyrrolidinyl)propionyl, 4-(3-butyl-1-pyrrolidinyl)butyryl, 2,2-dimethyl-3-(4-pentyl-2-pyrrolidinyl)propionyl, 5-(1-hexyl-3-pyrrolidinyl)pentanoyl, 6-(2,3-dimethyl-1-pyrrolidinyl)hexanoyl, 2-(2,3,4-trimethyl-1-pyrrolidinyl)acetyl, 3-(1-phenyl-2-pyrrolidinyl)propionyl, 2-(1-methyl-2-phenyl-3-pyrrolidinyl)propionyl, 2-(4-methyl-1-piperazinyl)acetyl, 2-(4-phenyl-1-piperazinyl)acetyl, 3-(4-ethyl-2-piperazinyl)propionyl, 2-(4-propyl-3-piperazinyl)propionyl, 4-(4-butyl-1-piperazinyl)butyryl, 2,2-dimethyl-3-(4-pentyl-2-piperazinyl)propionyl, 5-(4-hexyl-3-piperazinyl)pentanoyl, 6-(2,4-dimethyl-1-piperazinyl)hexanoyl, 2-(3,4,5-trimethyl-1-piperazinyl)acetyl, 2-(4-phenyl-3-methyl-1-piperazinyl)acetyl, 2-(4-methyl-1-piperidinyl)acetyl, 3-(1-ethyl-2-piperidinyl)propionyl, 2-(1-propyl-3-piperidinyl)propionyl, 4-(1-butyl-4-piperidinyl)butyryl, 2,2-dimethyl-3-(4-pentyl-1-piperidinyl)propionyl, 5-(1-hexyl-2-piperidinyl)pentanoyl, 6-(1-phenyl-3-piperidinyl)hexanoyl, 2-(2,5-dimethyl-4-phenyl-1-piperidinyl)acetyl, 2-(2,3,4-trimethyl-1-piperidinyl)acetyl, 2-(1,2-dimethyl-4-piperidinyl)acetyl, 2-(3-methyl-1-morpholinyl)acetyl, 3-(1-ethyl-2-morpholinyl)propionyl, 2-(1-propyl-3-morpholinyl)propionyl, 4-(2-butyl-1-morpholinyl)butyryl, 2,2-dimethyl-3-(1-pentyl-2-morpholinyl)propionyl, 5-(2-hexyl-3-morpholinyl)pentanoyl, 6-(3,5-dimethyl-1-morpholinyl)hexanoyl, 2-(2,3,5-trimethyl-1-morpholinyl)acetyl, 2-(3-phenyl-1-morpholinyl)acetyl, 2-(2-methyl-3-phenyl-1-morpholinyl)acetyl, and the like.

The "piperidinylcarbonyl which may optionally have a lower alkanoyl substituent" includes a piperidinylcarbonyl which may optionally have a substituent of a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, (1-piperidinyl)carbonyl, (2-piperidinyl)carbonyl, (3-piperidinyl)carbonyl, (4-piperidinyl)carbonyl, (1-acetyl-4-piperidinyl)carbonyl, (4-formyl-1-piperidinyl)carbonyl, (3-propionyl-2-piperidinyl)carbonyl, (1-butyryl-4-piperidinyl)carbonyl, (1-pentanoyl-4-piperidinyl)carbonyl, (1-hexanoyl-4-piperidinyl)carbonyl, and the like.

The carbostyril derivatives of the present invention can be prepared by various processes, for example, by the processes shown in the following reaction schemes. ##STR16## wherein R, q and R¹ are the same as defined above, and D is a group of the formula: --CH═CHR¹⁴ (R¹⁴ is a lower alkoxy, phenyl or a halogen atom), a group of the formula: ##STR17## (R¹⁵ and R¹⁶ are each a lower alkyl), or a group of the formula: --C.tbd.CH, and the D group may optionally be substituted by the group R¹.

The cyclization reaction of the compound of the formula (2) is carried out in an appropriate solvent or without solvent in the presence of an acid. The acid includes any conventional inorganic acids and organic acids, for example, inorganic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, etc.), Lewis acids (e.g. aluminum chloride, boron trifluoride, titanium tetrachloride, etc.), organic acids (e.g. formic acid, acetic acid, ethanesulfonic acid, p-toluenesulfonic acid, etc.), phosphorus pentoxide, polyphosphoric acid, among which hydrochloric acid, hydrobromic acid and sulfuric acid are preferable. The acid is usually used in at least equivalent amount, preferably in an amount of 10 to 50 times by weight, as much as the amount of the compound (2). The solvent includes any conventional inert solvents, for example, water, lower alcohols (e.g. methanol, ethanol, propanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, chlorobenzene, toluene, etc.), halogenated hydrocarbonss (e.g. methylene chloride, chloroform, carbon tetrachloride, etc.), acetone, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, and the like. The reaction is usually carried out at a temperature of from about 0° to about 200° C., preferably from room temperature to about 150° C., for about 5 minutes to 6 hours.

The reduction of the compound of the formula (1a) is usually carried out under conventional conditions for the usual catalytic reduction. The catalyst includes metals such as palladium, palladium-carbon, platinum, Raney nickel, etc. The solvent used therein includes, for example, alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), aliphatic hydrocarbons (e.g. hexane, cyclohexane, etc.), esters (e.g. ethyl acetate, etc.), fatty acids (e.g. acetic acid, etc.). The reduction reaction can be carried out at atmospheric pressure or under pressure, usually under atmospheric pressure to 20 kg/cm², preferably atmospheric pressure to 10 kg/cm². The reaction temperature is usually in the range of from about 0° C. to about 150° C., prefarably from room temperature to about 100° C.

The dehydration reaction of the compound of the formula (1b) is usually carried out in an appropriate solvent with an oxidizing agent. The oxidizing agent includes, for example, benzoquinones (e.g. 2,3-dichloro-5,6-dicyanobenzoquinone, chloranil (=2,3,5,6-tetrachlorobenzoquinone), etc.), halogenating agents (e.g. N-bromosuccinimide, N-chlorosuccinimide, bromine, etc.), hydrogenating catalysts (e.g. selenium oxide, palladium-carbon, palladium black, palladium oxide, Raney nickel, etc.). When a halogenating agent is used, it is usually used in an amount of 1 to 5 moles, peferably 1 to 2 moles, to 1 mole of the compound (1b). When a hydrogenating catalyst is used, it is used in a catalytic amount as usual. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, methoxyethanol, dimethoxyethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, cumene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), alcohols (e.g. butanol, amyl alcohol, hexanol, etc.), polar solvents (e.g. acetic acid, etc.), aprotic polar solvents (e.g. dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.). The reaction is usually carried out at a temperature of from room temperature to about 300° C., peferably from room temperature to about 200° C., for 1 to 40 hours. ##STR18## wherein R¹, q and R are the same as defined above, and R^(1') is hydrogen atom or a lower alkyl, provided that when R^(1') is a lower alkyl, q is 1 or 2.

The cyclization reaction of the compound (3) is carried out in an appropriate solvent in the presence of a condensation agent. The concensation agent includes, for example, Lewis acids, such as phosphorus pentoxide, hydrogen fluoride, sulfuric acid, polyphosphoric acid, aluminum chloride, zinc chloride, etc. The solvent includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g. diethyl ether, dioxane, etc.), aromatic hydrocarbons (e.g. nitrobenzene, chlorobenzene, etc.). The condensation agent is usually used in an amount of about 1 to 10 moles, peferably about 3 to 6 moles, to 1 mole of the compound (3). The reaction is usually carried out at a temperature of about 50° C. to about 250° C., peferably about 70° C. to about 200° C., for about 20 minutes to about 6 hours. ##STR19## wherein R, R¹, q, and the bond between 3- and 4-positions of the carbonstyril nucleus are the same as defined above.

The cyclization reaction of the compound (4) is carried out in an appropriate solvent or without using a solvent in the presence of an acid. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, polyphosphoric acid, etc.), organic acids (e.g. p-toluenesulfonic acid, ethanesulfonic acid, trifluoroacetic acid, etc.). The solvent includes any conventional solvents unless they affect on the reaction, for example, water, lower alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, tetrahydrofuran, dimethoxyethane, diphenyl ether, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The reaction is usually carried out at a temperature of from about -20° C. to about 150° C., preferably from about 0° C. to about 150° C., for about 5 minutes to about 30 hours. ##STR20## wherein R, R¹, q and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The reaction of the compound of the fomrula (5) and the compound of the formula (6) is usually carried out in an appropriate inert solvent in the presence or absence of a basic compound. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, N-methylpyrrolidone, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, etc. The basic compound includes, for example, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, triethylamine, etc.

The amounts of the compound (5) and the compound (6) are not critical, but the compound (6) is usually used at least in equimolar amount, preferably in an amount of 1 to 5 moles to 1 mole of the compound (5). The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably about 100° C. to about 180° C., for about 3 to 30 hours. In the above reaction, a copper powder may also be used as a catalyst, by which the reaction can proceed advantageously. ##STR21## wherein R¹, q, R³, m, n and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(2') is the same groups as R² other than hydrogen atom and a group of the formula: ##STR22## (R⁸ and R⁹ are the same as defined above).

The process of Reaction Scheme-5 is carried out by reacting a carbostyril derivative of the formula (1d) and a carboxylic acid compound of the formula (7) by a conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the conditions for the conventional amido bond producing reaction, for example,

(a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound (7) with an alkylhalocarboxylic acid to form a mixed acid anhydride and reacting the resultant with the amine compound (1d),

(b) an activated ester process, i.e. a process of converting the carboxylic acid compound (7) into an activated ester, such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and reacting the resultant with the amine compound (1d),

(c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound (7) and the amine compound (1d) in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, etc.,

(d) other processes, i.e. a process of converting the carboxylic acid compound (7) into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound (1d); a process of reacting an ester of the carboxylic acid compound (7) with a lower alcohol and the amine compound (1d) at a high temperature under high pressure; a process of reacting an acid halide compound of the carboxylic acid compound (7), i.e. a carboxylic acid halide, with the amine compound (1d), and the like.

The mixed acid anhydride used in the above mixed acid anhydride process is obtained by the known Schotten-Baumann reaction, and the reaction product is used without isolation from the reaction mixture for the reaction with the amine compound (1d) to give the desired compound of the formula (1e). The Schotten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used for the Schotten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), etc., and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is usually carried out at a temperature of from about -20° C. to about 100° C., preferably from about 0° C. to about 50° C., for about 5 minutes to about 10 hours, preferably about 5 minutes to about 2 hours.

The reaction of the thus obtained mixed acid anhydride with the amine compound (1d) is usually carried out at a temperature of from about -20° C. to about 150° C., preferably about 10° C. to about 50° C., for about 5 minutes to about 10 hours, preferably about 5 minutes to about 5 hours. The mixed acid anhydride process is usually carried out in an appropriate solvent. The solvent is any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The alkylhalocarboxylic acid used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, isobutyl chloroformate, and the like. In said process, the carboxylic acid compound (7), the alkylhalocarboxylic acid and the amine (1d) are usually used in each equimolar amount, but preferably, the alkylhalocarboxylic acid and the carboxylic acid compound (7) are used each in an amount of about 1 to 1.5 mole to 1 mole of the amine (1d).

Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound (1d), the reaction is usually carried out in the presence of a basic compound in an appropriate solvent. The basic compound is any conventional compounds and includes, in addition to the basic compounds used for the above-mentioned Schotten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride. etc. The solvent includes, in addition to the solvents used for the above-mentioned mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), acetonitrile, pyridine, acetone, and the like. The amount of the amine compound (1d) and the carboxylic acid halide is not critical, but the carboxylic acid halide is usually used at least in equimolar amount, preferably about 1 to 5 moles to 1 mole of the amine compound (1d). The reaction is usually carried out at a temperature of from about -20° C. to about 180° C., preferably from about 0° C. to about 150° C., for about 5 minutes to about 30 hours.

The amido bond producing reaction in the above Reaction Scheme-5 may also be carried out by reacting the carboxylic acid compound (7) and the amine (1d) in the presence of a condensation agent such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc. The reaction is usually carried out in the presence of the solvent and basic compound as used in the above reaction of the carboxylic acid halide and the amine (1d) at a temperature of from about -20° C. to about 150° C., preferably about 0° C. to about 100° C., for about 5 minutes to about 30 hours. The condensation agent and the carboxylic acid compound (7) are used at least in equimolar amount, preferably about 1 to 2 moles, to 1 mole of the amine (1d). ##STR23## wherein R¹, q, R³, m, n and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(8') is the same as R⁸ other than hydrogen atom.

The reaction of the compound (1d) and the compound (8) can be carried out in the presence or preferably absence of a basic compound in an appropriate solvent or without solvent. The solvent and the basic compound used therein are the same as the solvent and basic compound as used in the reaction of the carboxylic acid halide and the amine (1d) of the above Reaction Scheme-5. The compound (8) is usually used in an amount of about 1 to 5 moles, preferably about 1 to 3 moles, to 1 mole of the compound (1d). The reaction is usually carried out at a temperature of about 0° to 200° C., peferably from room temperature to about 150° C., for about 5 minutes to about 30 hours. In the above reaction, a boron compound (e.g. borone trifluoride etherate, etc.) may be added to the reaction system. ##STR24## wherein R¹, q, R¹¹, R¹² and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The reaction of the compound (9) and the compound (10) is carried out under the same conditions as used in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5. ##STR25## wherein R¹, q, X, l and the bond between 3- and 4-positions of carbostyril nucleus are the same as defined above, and R^(11') is hydrogen atom, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, a benzoyl which may optionally have a lower alkoxy substituent, tricyclo[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a cycloalkyl, R^(12a) is a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, tricyclo[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy substituent, or a cycloalkyl, and R^(12b) is a benzoyl which may optionally have a lower alkoxy substituent.

The reaction of the compound (1h) and the compound (11) is usually carried out in an inert solvent in the presence or absence of a basic compound. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol, etc.), acetic acid, ethyl acetate, acetone, acetonitrile, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, and the like. The basic compound includes, for example, carbonates (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodium methoxide, sodium ethoxide, etc.), and organic basic compounds (e.g. pyridine, ethyldiisopropylamine, dimethylaminopyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-(5) (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), etc.). The amount of the compound (1h) and the compound (11) is not critical, but the compound (11) is usually used at least in equivalent amount, preferably 1 to 5 moles, to 1 mole of the compound (1h). The reaction is usually carried out at a temperature of from about 0° C. to about 200° C., preferably from about 0° C. to about 170° C., for about 30 minutes to about 30 hours.

The reaction of the compound (1h) and the compound (12) is carried out under the same coniditons in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5.

In case of the compound of the formula (1) wherein R¹¹ and R¹² combine together with the nitrogen atom to which they bond to form a saturated or unsatrated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom and said heterocyclic group contains a secondary amino group, the compound can be converted into a compound where said heterocyclic group is substituted on said secondary amino group by a substituent selected from a phenyl(lower)alkyl and a phenyl having optionally a substituent selected from a lower alkoxy and a lower alkanoyl by treating it in the same manner as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8.

Besides, said compound can also be converted into a compound where the heterocyclic group is substitued on said secondary amine by a substituent selected from benzoyl and a lower alkanoyl by treating it in the same manner as in the reaction of the compound (1h) and the compound (12) in the above Reaction Scheme-8. ##STR26## wherein R¹, q, R³, m, n, R¹³, p, X, A, E, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(4') is hydrogen atom; a lower alkyl which may optionally be substituted by hydroxy or cyano; a lower alkenyl; a lower alkynyl; a phenyl(lower)alkyl; a lower alkanoyl which may optionally have one to three substitutents of a halogen atom; a benzoyl which phenyl ring may optionally be substituted by a member selected from nitro and an amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl; phenyl; a lower alkoxycarbonyl; a lower alkoxycarbonyl(lower)alkyl wherein the lower alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent; an amido having optionally a lower alkyl substituent; a pyrrolidinyl-substituted carbonyl which pyrrolidinyl ring may optionally be substituted by a phenyl(lower)alkoxycarbonyl; an amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl or a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent on the phenyl ring, a lower alkylsulfonyl, a lower alkanoyl, or a phenyl(lower)alkoxycarbonyl; a hydroxy-substituted lower alkanoyl; a lower alkanoyloxy(lower)alkanoyl; a lower alkylsulfonyl; a phenylsulfonyl which phenyl ring may optionally be substituted by nitro or an amino having optionally one or two substitutents selected from a lower alkyl and a lower alkanoyl; an amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally hydroxy substituent, imidazolyl, carbamoyl or a lower alkylthio, and the amido group may optionally have a lower alkyl substituent; an amino-substituted lower alkyl which may optionally have substituent selected from a lower alkyl and a lower alkanoyl; anilinocarbonyl; a piperidinyl which may optionally be substituted by a phenyl(lower)alkyl; a cycloalkyl, a cycloalkenylcarbonyl; a cycloalkylcarbonyl which may optionally have one to three substituents selected from hydroxy and a lower alkanoyloxy; a tetrahydropyranyl-substituted lower alkyl wherein the tetrahydropyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy; a lower alkanoyl which is substituted by a 5- or 6-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl and morpholino wherein the heterocyclic group may optionally have substituent selected from a lower alkyl and phenyl; a piperidinyl-substituted carbonyl which may optionally be substituted by a lower alkanoyl; a lower alkanoyloxy(lower)alkyl; a pyridyl-substituted lower alkyl; or an amino acid residue which can form an amido group with its amino group, R^(5a) is a lower alkyl which may optionally be substituted by hydroxy or cyano; a lower alkenyl; a lower alkynyl; a phenyl(lower)alkyl; phenyl; a lower alkoxycarbonyl(lower)alkyl wherein the lower alkyl moiety may optionally be substituted by hydroxy or an amino having optionally a phenyl(lower)alkoxycarbonyl substituent; an amido having optionally a lower alkyl substituent; a lower alkylsulfonyl; a phenylsulfonyl which phenyl ring may optionally be substituted by nitro or an amino having optionally one or two substitutents selected from a lower alkyl and a lower alkanoyl; an amido-substituted lower alkyl wherein the lower alkyl moiety have optionally a substituent selected from a phenyl having optionally hydroxy substituent, imidazolyl, carbamoyl or a lower alkylthio, and the amido group may optionally have a lower alkyl substituent; an amino-substituted lower alkyl which may optionally have a substituent selected from a lower alkyl and a lower alkanoyl; anilinocarbonyl; a piperidinyl which may optionally be substituted by a phenyl(lower)alkyl; a cycloalkyl, a tetrahydropyranyl-substituted lower alkyl wherein the tetrahydropyranyl ring may optionally have one to four substituents selected from hydroxy and a lower alkoxy; a lower alkanoyloxy(lower)alkyl; or a pyridyl-substituted lower alkyl, R^(5b) is a lower alkanoyl which may optionally have one to three substitutents of a halogen atom; a benzoyl which phenyl ring may optionally be substituted by a member selected from nitro and an amino having optionally one or two substituents selected from a lower alkyl, a lower alkanoyl and a phenyl(lower)alkoxycarbonyl; a lower alkoxycarbonyl; a pyrrolidinyl-substituted carbonyl which pyrrolidinyl ring may optionally be substituted by a phenyl(lower)alkoxycarbonyl; an amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally be substituted by a member selected from phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substitutent, carbamoyl, imidazolyl or a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substitutent, a lower alkenyl, a lower alkanoyl, or a phenyl(lower)alkoxycarbonyl; a hydroxy-substituted lower alkanoyl; a lower alkanoyloxy(lower)alkanoyl; a cycloalkenylcarbonyl; a cycloalkylcarbonyl which may optionally have one to three substituents selected from hydroxy and a lower alkanoyloxy; a lower alkanoyl which is substituted by a 5- or 6-membered saturated heterocyclic group selected from pyrrolidinyl, piperazinyl, piperidinyl and morpholino wherein the heterocyclic group may optionally be substituted by a lower alkyl or phenyl; a piperidinyl-substituted carbonyl which may optionally be substituted by a lower alkanoyl; or an amino acid residue which can form an amido group with its amino group, p' and p" are each an integer of 1 to 3, provided that p+p' and p+p" are each an integer not more than 3. ##STR27## wherein R¹, q, R³ , m, n, R¹³, p, X, B, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(6') is hydrogen atom, a lower alkyl, a lower alkanoyl having optionally one to three halogen substituents, a lower alkoxycarbonyl, a carboxy(lower)alkyl, a lower alkoxycarbonyl(lower)alkyl, a lower alkenyl, an amido-substituted lower alkyl having optionally a lower alkyl substituent, or a phenyl(lower)alkoxycarbonyl, R^(7a) is a lower alkyl, a lower alakoxycarbonyl(lower)alkyl, carboxy(lower)alkyl, a lower alkenyl, or an amido-substituted lower alkyl having optionally a lower alkyl substituent, R^(7b) is a lower alkanoyl having optionally one to three halogen substitituents, a lower alkoxycarbonyl, or a phenyl(lower)alkoxycarbonyl, p' and p" are each an integer of 1 to 3, provided that p+p' and p+p" are each an integer not more than 3.

The reaction of the compound (1k) and the compound (14) in the Reaction Scheme-9A and the reaction of the compound (1n) and the compound (16) in the Reaction Scheme-9B can be carried out under the same conditions as in the reaction of the compound (1h) and the compound (12) in the above Reaction Scheme-8.

Besides, the compound (1m) wherein R^(5b) is a lower alkanoyl or the compound (1p) wherein R^(7b) is a lower alkanoyl having optionally one to three substituents of a halogen atom can also be obtained by reacting the compound (1k) or the compound (1n) with an alkanoylating agent of the formula: (R^(5b) ')₂ O or (R^(7b'))₂ O (wherein R^(5b') is a lower alkanoyl, and R^(7b') is a lower alkanoyl having optionally one to three substituents of a halogen atom) in an appropriate solvent or without solvent in the presence or absence, peferably presence, of a basic compound. The solvent includes, for example, the above-mentioned aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol, etc.), dimethylformamide, dimethylsulfoxide, and further halogenated hydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone, pyridine, etc. The basic compound includes, for example, tertiary amines (e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassium hydroxide, sodium hydride, and the like. The above reaction can also be carried out in a solvent such as acetic acid in the presence of a mineral acid (e.g. sulfuric acid, etc.). The alkanoylating agent is usually used in an equimolar amount or more, preferably 1 to 10 moles, to 1 mole of the staring compound, and the reaction is usually carried out at a temperature of about 0° C. to about 200° C., preferably from about 0° C. to about 150° C., for about 0.5 to 15 hours.

Moreover, the compound (1l) wherein R^(5a) is a lower alkyl or a phenyl(lower)alkyl) and the compound (1o) wherein R^(7a) is a lower alkyl can also be obtained by reacting the compound (1k) or the compound (1n) with a compound of the formula: R¹⁸ --CO--R¹⁹ (18) (wherein R¹⁸ and R¹⁹ are each hydrogen atom, phenyl, or a lower alkyl), respectively. In case of the compound (1n), however, the compound to be reacted should be the compound (18) wherein R¹⁸ and R¹⁹ are other than phenyl. The reaction is usually carried out in an appropriate solvent or without solvent in the presence of a reducing agent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reducing agent includes, for example, formic acid, fatty acid alkali metal salts (e.g. sodium formate, etc.), hydrogenating reducing agents (e.g. sodium boro hydride, sodium cyanoboro hydride, lithium aluminum hydride, etc.), catalystic reducing agents (e.g. palladium black, palladium-carbon, platinum oxide, platinum black, Raney nickel, etc.). When formic acid is used as the reducing agent, the reaction is usually carried out at a temperature of from room temperature to about 200° C., peferably about 50° C. to about 150° C., for about 1 to 10 hours. The formic acid is usually used in a large excess amount to the compound (1k) or the compound (1n).

When a hydrogenating reducing agent is used, the reaction is usually carried out at a temperature of about -30° C. to about 100° C., preferably about 0° C. to about 70° C., for about 30 minutes to about 12 hours. The reducing agent is usually used in an amount of 1 to 20 moles, preferably 1 to 6 moles, to 1 mole of the compound (1k) or the compound (1n). When lithium aluminum hydride is used as the reducing agent, it is preferable to use a solvent selected from ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme, etc.) and aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.).

When a catalytic reducing agent is used, the reaction is usually carried out under atmospheric pressure to about 20 atm., preferably atmospheric pressure to about 10 atm. under hydrogen atmosphere or in the presence of a hydrogen donor (e.g. formic acid, ammonium formate, cyclohexene, hydrazine hydrate, etc.) at a temperature of about -30° C. to about 100° C., preferably about 0° C. to about 60° C., for about 1 to 12 hours. The catalytic reducing agent is usually used in an amount of about 0.1 to 40% by weight, preferably about 1 to 20% by weight, of the amount of the compound (1k) or the compound (1n). The compound (18) is usually used at least in equivalent amount, preferably equivalent to a large excess amount, to the compound (1k) or the compound (1n).

In case of the compound of the formula (1) wherein R⁶ and R⁷ combine together with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated or unsatrated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom and said heterocyclic group contains a secondary amino group, and/or R⁴ and R⁵ combine together with the nitrogen atom to which they bond to form a 5- or 6-membered, saturated heterocyclic group which may be intervened or not with nitrogen, oxygen or sulfur atom and said heterocyclic group contains a secondary amino group, the compound can be converted into a compound where said heterocyclic groups are substituted on said secondary amino group by a substituent selected from a lower alkyl (in case of forming a heterocyclic group by R⁶ and R⁷) or a phenyl having optionally a substituent selected from a halogen atom and a lower alkoxy (in case of forming a heterocyclic group by R⁴ and R⁵) by treating it in the same manner as in the reaction of the compound (1k) and the compound (14) in the above Reaction Scheme-9A.

Besides, said compound (where R⁶ and R⁷ form a heterocyclic group) can also be converted into a compound where the heterocyclic group is substitued on said secondary amino group by a substituent selected from a lower alkoxycarbonyl by treating it in the same manner as in the reaction of the compound (1k) and the compound (15) in the above Reaction Scheme-9A. ##STR28## wherein R¹, q, R³, m, n, p', p", and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(13a) is the same groups as R¹³ provided that at least one of the R^(13a) is cyano, and R^(13b) is the same groups as R¹³ provided that at least one of the R^(13b) is amidino. ##STR29## wherein R¹, q, R³, m, n, p', p", and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(13c) is the same groups as R¹³ provided that at least one of the R^(13c) is a cyano-substituted lower alkoxy, and R^(13d) is the same groups as R¹³ provided that at least one of the R^(13d) is an amidino-substituted lower alkoxy.

The reaction of converting the compound (1q) to the compound (1r) in the above Reaction Scheme-10A and of converting the compound (1s) to the compound (1t) in the above Reaction Scheme-10B is carried out by reacting the compound (1q) and the compound (1s) with various alcohols, phenols, and thiols, respectively in an appropriate solvent or without solvent in the co-presence of a basic compound and hydrogen chloride, followed by reacting the resultant imidate compound with aqueous ammonia in an appropriate solvent. The solvent used in the reaction for obtaining an imidate compound includes, for example, halogenated hydrocarbons (e.g. dichloromethane, chloroform, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), and the like. The alcohols used therein include, preferably lower alcohols such as methanol, ethanol, etc. These alcohols are usually used in an amount of 1 mole or more, peferably 1 to 2 moles, to 1 mole of the starting compound. The basic compound includes, preferably metal alcoholates such as sodium methylate, sodium ethylate, etc., particularly preferably the alcoholates with the same alcohols as above. The reaction for forming imidate compound is usually carried out at a temperature of about -10° C. to about 50° C., preferably about 0° C. to room temperature, for about 1 to 200 hours. The imidate compound thus obtained can be used in the subsequent reaction without being isolated from the reaction mixture.

The solvent used in the reaction of converting the imidate compound to the desired amidine compound includes, for example, water soluble solvents such as lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetone, dimethylformamide, acetonitrile, and the like. The aqueous ammonium used in the reaction is usally used in an amount of 1 mole or more, preferably 5 to 50 moles, to 1 mole of the imidate compound. The reaction is usually carried out at a temperature of about 0° C. to about 100° C., preferably 0° C. to room temperature, for about 10 minutes to about 15 hours. In the above reaction of converting the imidate compound to the amidine compound, there may occasionally be produced a compound where R^(13d) is the same groups as R¹³ provided that at least one of the R^(13d) is a carbamoyl-substituted lower alkoxy, or R^(13b) is the same groups as R¹³ provided that at least one of R^(13b) is a carbamoyl group, but these compounds can easily be separated from the reaction system. ##STR30## wherein R¹, q, R³, m, n, R¹³, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R²⁰ and R²¹ are each lower alkoxy, and pa is 0 or an integer of 1 to 2.

The reaction of the compound (1u) and the compound (19) can be carried out in an appropriate solvent in the presence of an acid. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl keton, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.). The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 0.5 to 5 hours The compound (19) is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the compound (1u). ##STR31## wherein R¹, q, R³, m, n, R⁴, R⁵, R¹³, p, p', p", X, A, E, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above. ##STR32## wherein R¹, q, R³, m, n, R⁶, R⁷, R¹³, p, p', p", X, B, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above. ##STR33## wherein R¹, q, R³, m, n, R¹³, p, p', p", X, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and D is a lower alkylene, R²² is a group of the formula: ##STR34## (R³² and R³³ are the same as defined above), benzoyloxy, a lower alkylsulfonyloxy, a lower alkanoyloxy, a lower alkylthio, benzimidazolylthio, pyrimidylthio, an imidazolylthio having optionally a lower alkyl substituent, a phenylthio having optionally a substituent selected from nitro and amino on the phenyl ring, pyridylthio, or pyrrolyl, R²³ is hydroxy, a lower alkoxy, benzoyloxy, a lower alkylsulfonyloxy, a lower alkanoyloxy, or a lower alkoxy having one or two substituents selected from cyano, hydroxy and an amino having optionally a lower alkyl substituent, R²⁴ is the same as the above R²² or R²³, and M is an alkali metal (e.g. potassium, sodium, etc.). ##STR35## wherein R¹, q, R³, m, n, R¹³, p, p', p", X, M and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and D' is a lower alkylene.

The reaction of the compound (1w) and the compound (20) in Reaction Scheme-12A, of the compound (1y) and the compound (21) in Reaction Scheme-12B, of the compound (1A) and the compound (22) or (23) in Reaction Scheme-12C, and of the compound (1A') and teh compound (23a) in Reaction Scheme-12D is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. ##STR36## wherein R¹, q, R³, m, n, R¹³, p, p', p", A, E, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The reaction of converting the compound (1C) into the compound (1D) can be carried out by reacting the compound (1C) with hydrazine in an appropriate solvent or by hydrolyzing the compound (1C). The solvent used in the reaction with hydrazine includes the same solvent as used in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. The reaction is usually carried out at a temperature of from room temperature to about 120° C., preferably about 0° C. to about 100° C., for about 0.5 to 5 hours. Hydrazine is usually used in an amount of at least 1 mole, preferably about 1 to 5 moles, to 1 mole of the compound (1C). The hydrolysis is carried out under the same conditions as in the hydrolysis of the compound (1) wherein R⁴ or R⁵ is a lower alkoxycarbonyl as described hereinafter. ##STR37## wherein R¹, q, R³, m, n, R¹³, p, p', p", X, D, M, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R²⁵ is a lower alkanoyl, a lower alkenyl, a lower alkyl, a lower alkylsulfonyl, a lower alkyl having one or two substituents selected from hydroxy and an amino having optionally a lower alkyl substituent, or benzoyl, R²⁶ is a group of --OCN, and R²⁷ is the same groups as the above R²⁵ or a carbamoyl.

The reaction of the compound (1E) and the compound (24) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. In said reaction, an alkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may be added to the reaction system.

The reaction of the compound (1E) and the compound (25) is carried out in an appropriate solvent in the presence of an acid. The solvent includes the same solvents as used in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. In addition thereto, there may also be used halogenated hydrocarbons (e.g. methylene chloride, chloroform, carbon tetrachloride, etc.). The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. formic acid, acetic acid, trifluroacetic acid, aromatic sulfonic acids, etc.). The reaction is usually carried out at a temperature of about 0° C. to about 150° C., preferably, from room temperature to about 100° C., for about 1 to 15 hours. The compound (25) is usually used in an amount of 1 to 5 moles, preferably 1 to 3 moles, to 1 mole of the compound (1E). ##STR38## wherein R¹, q, R³, m, n, R¹³, p, p', p", A, E, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R²⁸ is hydrogen atom, phenyl or a lower alkyl.

The reaction of the compound (1D) and the compound (26) is carried out under the same conditions as in the reaction of the compound (1d) and the compound (8) in the above Reaction Scheme-6. ##STR39## wherein R, X, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R²⁹ is hydrogen atom, a lower alkanoyl, a lower alkyl or benzoyl, R³⁰ is a lower alkyl, and R³¹ is a lower alkanoyl or benzoyl.

The reaction of the compound (1F) and the compound (27) is carried out under the same conditions as in the reaction of the compound (1k) and the compound (14) in the above Reaction Scheme-9A.

The reaction of the compound (1F) and the compound (28) is carried out under the same conditions as in the reaction of the compound (1k) and the compound (15) in the above Reaction Scheme-9A. ##STR40## wherein R and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The nitration of the compound (lI) can be carried our under the same conditions as used in the conventional nitration reaction of an aromatic compound. That is, it can be carried out by using a nitrating agent in an appropriate inert solvent or without solvent. The inert solvent includes, for example, acetic acid, acetic anhydride, conc. sulfuric acid, and the like. The nitrating agent includes, for example, fuming nitric acid, conc. nitric acid, mixed acid (e.g. a mixture of nitric acid with sulfuric acid, fuming sulfuric acid, phosphoric acid, or acetic anhydride), a mixture of an alkali metal nitrate (e.g. potassium nitrate, sodium nitrate, etc.) with sulfuric acid, and the like. The nitrating agent is used in an equimolar amount or more, usually in an excess amount, to the amount of the starting compound. The reaction is advantageously carried out at a temperature of about 0° C. to room temperature for about 0.5 to 4 hours. ##STR41## wherein R¹, q, R, and X are the same as defined above.

The cyclization reaction of the compound (1K) is so-called Friedel Craft reaction and is usually carried out in an appropriate solvent in the presence of a Lewis acid. The solvent includes any conventional solvent which is usually used in this kind of reaction, for example, carbon disulfide, nitrobenzene, chlorobenzene, dichloromethane, dichloroethane, trichloroethane, tetrachloroethane, and the like. The Lewis acid includes any conventional acid, for example, aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, boron trifluoride, conc. sulfuric acid, and the like. The amount of Lewis acid is not critical but is usually in the range of about 2 to 6 moles, preferably about 3 to 4 moles, to 1 mole of the compound (1K). The reaction temperature is usually in the range of about 20° C. to 200° C., preferably 40° C. to 180° C. The reaction period of time may vary depending on the kinds of the starting compound, catalyst and reaction temperature, etc., but is usually in the range of about 0.5 to 6 hours. Besides, sodium chloride may be added to the reaction system in order to proceed the reaction advantageously. ##STR42## wherein R¹, q, R³, m, n, p', p", and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(13e) is the same groups as R¹³ provided that at least one of the R^(13e) is a lower alkenyloxy, R^(13f) is the same groups as R¹³ provided that at least one of the R^(13f) is an oxilanyl-substituted lower alkoxy, R^(13g) is the same groups as R¹³ provided that at least one of the R^(13g) is a lower alkoxy having a substituent selected from hydroxy and a group of the formula: ##STR43## (R³² and R³³ are as defined above), and p"' is an integer of 1 to 3.

The reaction of converting the compound (M) into the compound (N) is carried out under the same conditions as in the reaction of oxidizing lower alkylthio into lower alkylsulfonyl as mentioned above. The reaction of the compound (1N) and the compound (29) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. Besides, the hydrolysis of the compound (1N) can be carried out under the same conditions as in the hydrolysis of the compound (1) where R⁴ or R⁵ is a lower alkoxycarbonyl to convert into a compound (1) where R⁴ or R⁵ is hydrogen atom as described hereinafter. ##STR44## wherein R¹, q, R³, m, n, p', p", p"', and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(13h) is the same groups as R¹³ provided that at least one of the R^(13h) is a lower alkanoyl, R^(13i) is the same groups as R¹³ provided that at least one of the R^(13i) is a lower alkenyl having optionally a substituent selected from a lower alkoxycarbonyl, carboxyl or hydroxy, R^(13j) is the same groups as R¹³ provided that at least one of the R^(13j) is a lower alkyl having optionally a substituent selected from a lower alkoxycarbonyl, carboxyl and hydroxy.

The reaction of converting the compound (1P) into the compound (1Q) is carried out in an appropriate solvent in the presence of a Wittig reagent and a basic compound. The Wittig reagent includes, for example, a phosphoric compound of the formula:

    [(R.sup.34).sub.3 P.sup.+ --CH.sub.2 --R.sup.35 ]X.sup.-   (A)

wherein R³⁴ is phenyl, R³⁵ is a lower alkyl having optionally a substituent selected from a lower alkoxycarbonyl, carboxyl and hydroxy, and X is a halogen atom, and a phosphoric compound of the formula: ##STR45## wherein R³⁶ is a lower alkoxy, and R³⁷ is a lower alkyl.

The basic compound includes inorganic bases (e.g. metallic sodium, metallic potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc.), metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), alkyl or aryl lithiums or lithium amides (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, etc.), organic bases (e.g. pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, etc.). The solvent includes any solvent which does not affect on the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and the like. The reaction is usually carried out at a temperature of about -80° C. to about 150° C., preferably about -80° C. to about 120° C., for about 0.5 to 15 hours.

The reaction of converting the compound (1Q) into the compound (1R) is carried out under the same conditions as in the catalytic hydrogenation as described herebefore.

The starting compound (2) can be prepared, for example, by the processes as shown in the following Reaction Schemes-21 and -22. ##STR46## wherein R¹, q, R², R³, m, n and D are the same as defined above, provided that the group R¹ may substitute on either of the benzene ring or the group D of the compound (2a).

The reaction of the compound (30) and the compound (31) is carried out under the same conditions as in the reaction of the compound (1k) and the compound (18) in the above Reaction Scheme-9A.

The reaction of the compound (32) and the compound (33) is carried out under the same conditions as in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5. ##STR47## wherein R¹, q, R¹⁰, and D are the same as defined above, provided that the group R¹ may substitute on either of the benzene ring or the group D of the compound (2b).

The reaction of the compound (34) and the compound (33) is carried out under the same conditions as the above reaction of the compound (32) and the compound (33).

The starting compound (3) can be prepared, for example, by the process of the following Reaction Scheme-23. ##STR48## wherein R¹ and R are the same as defined above, R³⁸ is hydrogen atom or a lower alkyl, and r is 1 or 2.

The reaction of the compound (35) and the compound (36) is carried out in a solvent as used in the reaction of the compound (1E) and the compound (25) in the above Reaction Scheme-14. The compound (36) is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the compound (35). The reaction is usually carried out at a temperature of 0° C. to 150° C., preferably from room temperature to about 100° C., for about 0.5 to 5 hours.

The starting compound (4) can be prepared, for example, by the process of the following Reaction Scheme-24. ##STR49## wherein R¹, q, R², R³, m, and n are the same as defined above.

The reaction of the compound (37) and the compound (31) is carried out under the same conditions as in the reaction of the compound (30) and the compound (31) in the above Reaction Scheme-21.

The staring compound (1K) can be prepared, for example, by the process of the following Reaction Scheme-25. ##STR50## wherein R¹, q, r, R and X are as defined above, provided that the total of q and r is not more than 3.

The reaction of the compound (35) and the compound (38) is carried out under the same conditions as in the reaction of the compound (32) and the compound (33) in the above Reaction Scheme-21. ##STR51## wherein R¹, r and R are as defined above, and R³⁹ is a lower alkyl.

The reaction of the compound (39) and the compound (40) is carried out in an appropriate solvent in the presence of a basic compound. The basic compound includes, inorganic bases (e.g. sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium carbonate, sodium hydride, etc.), alkali metal alcoholates (e.g. sodium methylate, sodium ethylate, etc.), and organic bases (e.g. triethylamine, pyridine, α-picoline, N,N-dimethylaniline, N-methylmorpholine, piperidine, pyrrolidine, etc.). The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), polar solvents (e.g. dimethylsulfoxide, dimethylformamide, etc.), and the like. The reaction is usually carried out at a temperature of from room temperature to 150° C., preferably from 60° C. to 120° C., for about 1 to 24 hours. The compound (40) is usually used in an equimolar to large excess amount, preferably 1 to 5 moles to 1 mole of the compound (39). A lower alkane (e.g. acetic acid, etc.) or molecular sieves may be added to the reaction system to proceed the reaction advantageously.

The compound (39) can be prepared, for example, by the process of the following reaction scheme. ##STR52## wherein R¹, q, R², R³, m and n are as defined above.

The reaction of the compound (41) and the compound (31) is carried out under the same conditions as in the reaction of the compound (30) and the compound (31) in the above Reaction Scheme-21.

The reaction of converting the compound (42) into the compound (39a) is carried out in an appropriate solvent or without solvent in the presence of an oxidizing agent. The solvent includes the above-mentioned aromatic hydrocarbons, lower alcohols, halogenated hydrocarbons, ethers, polar solvents (e.g. dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, etc.). The oxidizing agent includes acetic anhydride-dimethylsulfoxide, phosphorus pentoxide-dimethylsulfoxide, sulfur trioxide.pyridine complex-dimethylsulfoxide, dicyclohexylcarbodiimide-dimethylsulfoxide, oxalyl chloride-dimethylsulfoxide, chromic acid, chromic acid complexes (e.g. chromic acid-pyridine complex, chromic acid-2-pyridine complex, etc.), manganese dioxide, and the like. When oxayl chloride-dimethylsulfoxide is used as the oxidizing agent, there may be added to the reaction system the basic compound as used in the reaction of the compound (1d) and the carboxylic halide in the above Reaction Scheme-5. The reaction is usually carried out at a temperature of 0° C. to 150° C., preferably from room temperature to about 100° C., for about 1 to 30 hours. The oxidizing agent is usually used in an amount of 1 to 20 moles, preferably 1 to 15 moles, to 1 mole of the compound (42). ##STR53## wherein R¹, q, R³, m, n, R¹³, pa, A, R²⁰, R²¹ and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The reaction of the compound (1S) and the compound (19) is carried out under the same conditions as in the reaction of the compound (1u) and the compound (19) in the above Reaction Scheme-11. ##STR54## wherein R¹, q, R³, m, n, R⁸, X, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R⁴⁰ is hydrogen atom, a lower alkyl or a lower alkanoyl, R⁴¹ is a lower alkyl, R⁴² is a lower alkanoyl, R⁴³ is a lower alkoxy, a halogen atom, an amino having optionally one or two substituents selected from a lower alkyl and a lower alkanoyl, or nitro, t is 0, 1 or 2, s is an integer of 1 to 3, provided that total of t and s is not more than 3.

The reaction of the compound (1U) and the compound (43) is carried out under the same conditions as in the reaction of the compound (1k) and the compound (14) in the above Reaction Scheme-9A.

The reaction of the compound (1U) and the compound (44) is carried out under the same conditions as in the reaction of the compound (1k) and the compound (15) in the above Reaction Scheme-9A. ##STR55## wherein R¹, q, R³, m, n, R¹³, pa, D, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above.

The reaction of the compound (1X) and the compound (45) is carried out in an appropriate solvent or withtout solvent in the presence of an acid. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, phosphorus pentoxide, polyphosphoric acid, etc,), and organic acids (e.g. p-toluenesulfonic acid, ethanesulfonic acid, methanesulfonic acid, trifluoroacetic acid, etc.), or a mixture of these acids. The solvent includes the same solvents as used in the cyclization reaction of the compound (4) in the above Reaction Scheme-3. The compound (45) is usually used in an amount of at least 1 mole, preferably 1 to 1.5 mole, to 1 mole of the compound (1x). The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 1 to 5 hours. ##STR56## wherein R, R¹ and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R^(1a) is a lower alkoxycarbonyl, R^(1b) is hydrazinocarbonyl, R^(1c) is carboxyl, R^(1d) is a phenyl(lower)alkoxycarbonyl-substituted amino, and r is 1 or 2.

The reaction of the compound (1aa) and hydrazine is carried out in an appropriate solvent. The solvent includes the same solvents as used in the reaction of the compound (1d) and the halide (7) in the above Reaction Scheme-5. Hydrazine is used in a large excess amount, preferably in 8 to 20 moles to 1 mole of the compound (1aa). The reaction is usually carried out at a temperature of from room temperature to about 150° C., preferably from room temperature to about 100° C., for about 1 to 10 hours.

The reaction of converting the compound (1aa) into the compound (1cc) is carried out under the same conditions as in the hydrolysis of the compound (1) where R⁴ or R⁵ is a lower alkoxycarbonyl to convert into a compound (1) where R⁴ or R⁵ is hydrogen atom as described hereinafter.

The reaction of converting the compound (1bb) into the compound (1dd) is carried out by reacting the compound (1bb) with a metal nitrite (e.g. sodium nitrite, potassium nitrite, etc.) in an appropriate solvent in the presence of an acid, followed by reacting the resultant with a phenyl lower alcohol (e.g. benzyl alcohol, α-phenethyl alcohol, β-phenethyl alcohol, etc.). The acid used therein includes, for example, hydrochloric acid, hyrobromic acid, sulfuric acid, tetrafluoroboric acid, hexafluorophosphoric acid, and the like. The solvent used in the reaction with a metal nitrite includes, for example, water, dichloromethane, chloroform, carbon tetrachloride or a mixture of these solvents. The reaction is usually carried out at a temperature of about -20° C. to about 10° C., preferably about -5° C. to about 5° C., for about 5 minutes to about one hour. The nitrite is usually used in an amount of at least 1 mole, preferably 1 to 1.5 mole, to 1 mole of the compound (1bb). The solvent used in the reaction with a phenyl lower alcohol includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, etc.), and the like. The reaction is carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 0.5 to 10 hour. The phenyl lower alcohol is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the compound (1bb).

The reaction of converting the compound (1dd) into the compound (1ee) is carried out under the same conditions as in the reduction reaction of the compound (1) wherein R² is a heterocyclic group-substituted carbonyl having a phenyl(lower)alkoxycarbonyl on at least one nitrogen atom thereof as described hereinafter. ##STR57## wherein R¹, q, R, R³⁴, and X are the same as defined above, and R⁴⁴ is a lower alkoxycarbonyl.

The reaction of the compound (39) and the compound (46) is carried out under the same conditions as in the reaction of converting the compound (1P) into the compound (1Q) in the above Reaction Scheme-20.

The cyclization reaction of the compound (47) is carried out in the presence of a catalytic reducing agent and in the presence or absence of a basic compound or an acid, preferably in the presence of an acid, in an appropriate solvent. The basic compound includes, for example, organic bases (e.g. triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, DBN, DBU, DABCO, etc.), and inorganic bases (e.g. potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, potassium hydrogen carbonate, sodium hydrogen carbonate, etc.), and the acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, phosphoric acid, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these acids. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-emthoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, or a mixture of these solvents. The catalytic reducing agent includes the same catalysts as used in the reduction reaction of the compound (1a) in the above Reaction Scheme-1. The reaction is usually carried out under atmospheric pressure to about 20 kg/cm², preferably atmospheric pressure to about 10 kg/cm², at a temperature of about 0° C. to about 200° C., preferably from room temperature to about 150° C., for about 1 to 10 hours. The catalytic reducing agent is preferably used in an amount of 0.02 to 1 part by weight to 1 part of the compound (47). ##STR58## wherein R¹, q, R³, m, n, R¹³, R^(4'), p', p", A, E, l, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R⁴⁵ is a lower alkanoyl which has one halogen substituent and may optionally have a further substituent selected from a phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substituent, carbamoyl, imidazolyl and a lower alkylthio, R⁴⁶ is an amino which may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substituent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent, a lower alkylsulfonyl, a lower alkanoyl, and a phenyl(lower)alkoxycarbonyl, and R⁴⁷ is an amino-substituted lower alkanoyl wherein the lower alkanoyl moiety may optionally have a substituent selected from a phenyl(lower)alkoxycarbonylamino, hydroxy, a phenyl having optionally a hydroxy substituent, carbamoyl, imidazolyl, and a lower alkylthio, and the amino group may optionally have a substituent selected from a lower alkyl having optionally a hydroxy substituent, a lower alkenyl, a phenyl(lower)alkyl having optionally a lower alkoxy substituent, a lower alkylsulfonyl, a lower alkanoyl, and a phenyl(lower)alkoxycarbonyl.

The reaction of the compound (1gg) and the compound (48) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. ##STR59## wherein R², R³, m, and n are the same as defined above.

The reaction of the compound (49) and the compound (50) is carried out by heating them in an appropriate solvent. The solvent includes, for example, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetonitrile, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably about 50° C. to about 150° C., for about 1 to 10 hours. The compound (50) is usually used in an amount of at least 1 mole, preferably 1 to 1.5 mole, to 1 mole of the compound (49).

The reaction of the compound (51) and the compound (52) is usually carried out without using any solvent at a temperature of about 50° C. to about 200° C., preferably from about 50° C. to about 150° C., for about 1 to 10 hours.

The reaction of converting the compound (53) into the compound (1bb) is carried out in an appropriate solvent in the presence of a halogenating agent and a basic compound. The solvent includes, for example, halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), alcohols (e.g. methanol, ethanol, propanol, etc.), and the like. The halogenating agent includes N-halogenated succinimides (e.g. N-bromosuccinimide, N-chlorosuccinimide, etc.), halogen molecules (e.g. bromine, chlorine, etc.), N-bromoacetamide, pyrrolidinium bormide perbromide, and the like. The basic compound includes the compounds as used in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. The reaction is usually carried out at a temperature of about 0° C. to about 150° C., preferably from room temperature to about 100° C., for about 1 to 10 hours. The halogenating agent is usually used in an amount of at least 1 mole, preferably 1 to 3 moles, to 1 mole of the compound (53). ##STR60## wherein R¹, r, R², R³, m, n, X, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R⁴⁸ is a lower alkyl, and R⁴⁹ is a lower alkanoyl.

The reaction of the compound (1jj) and the compound (54) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8.

The reaction of the compound (1jj) and the compound (55) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (12), wherein a carboxylic halide is used, in the above Reaction Scheme-8, and the reaction of the compound (1jj) and the compound (56) is carried out under the same conditions as in the reaction of the compound (1k) and the compound of the formula: (R^(5b'))₂ O in the above Reaction Scheme-9A. ##STR61## wherein R¹, q, n, R and X are as defined above.

The reaction of the compound (57) and the compound (58) is carried out under the same conditions as in the reaction of the compound (5) and the compound (6) in the above Reaction Scheme-4. In this reaction, copper monoxide may be added to the reaction system in order to proceed the reaction advantageously.

The reaction of converting the compound (59) into the compound (42) can be carried out under the same conditions as used in the reduction reaction of the compound (1) wherein R¹³ is a lower alkanoyl or benzoyl as described hereinafter.

In case of the compounds of the formula (1) wherein (a) R² is a phenyl(lower)alkanoyl wherein the lower alkanoyl moiety is substituted by an amino having a lower alkoxycarbonyl substituent, (b) R⁴ or R⁵ is a lower alkoxycarbonyl, (c) R⁶ or R⁷ is a lower alkoxycarbonyl, or (d) R⁶ and R⁷ form a heterocyclic group which has a lower alkoxycarbonyl substituent on at least one nitrogen atom of the heterocyclic group, these compound can be subjected to hydrolysis to obtain the corresponding compounds of the formula (1) wherein (a) R² is a phenyl(lower)alkanoyl wherein the lower alkanoyl moiety is substituted by an amino, (b) R⁴ or R⁵ is hydrogen atom, (c) R⁶ or R⁷ is hydrogen atom, or (d) R⁶ and R⁷ form a heterocyclic group where at least one nitrogen has no substituent, respectively.

The hydrolysis can be carried out in an appropriate solvent or without solvent in the presence of an acid or a basic compound. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.). The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydoxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 0.5 to 25 hours.

In the case of the compounds of the formula (1) wherein R² is a heterocyclic group-substituted carbonyl which has a phenyl(lower)alkoxycarbonyl on at least one nitrogen atom thereof; R¹³ is a benzoyl which is substituted by at least one amino group having at least one phenyl(lower)alkoxycarbonyl substituent on the phenyl ring; R⁴ or R⁵ is a pyrrolidinylcarbonyl having at least one phenyl(lower)alkoxycarbonyl substituent on the nitrogen atom of the pyrrolidine ring, or an amino-substituted lower alkanoyl wherein the amino has at least one phenyl(lower)alkoxycarbonyl susbtituent and the lower alkanoyl moiety may optionally have a substituent; or R⁶ or R⁷ is a phenyl(lower)alkoxycarbonyl, these compounds can be subjected to a reduction reaction to obtain the corresponding compounds of the formula (1) wherein R² is a heterocyclic group-substituted carbonyl wherein at least one nitrogen has hydrogen substituent; R¹³ is a benzoyl which has at least one amino group having no phenyl(lower)alkoxycarbonyl substituent; R⁴ or R⁵ is a pyrrolidinylcarbonyl having no substituent on the nitrogen atom thereof or an amino-substituted lower alkanoyl having no substituent on the amino group thereof; or R⁶ or R⁷ is hydrogen atom. The reduction is carried out by catalytic reduction in an appropriate solvent in the presence of a catalyst. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvent (e.g. N,N-dimethylformamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 part by weight to 1 part by weight of the starting compound. The reaction is usually carried out at a temperature of about -20° C. to about 100° C., preferably from about 0° C. to about 80° C., under atmospheric pressure to 10 atm., for about 0.5 to 20 hours.

The compound of the formula (1) wherein R¹³ is a phenyl(lower)alkoxy can be converted into the corresponding compound (1) wherein R¹³ is hydroxy by reduction thereof. The reduction can be carried out under the same conditions as in the reduction of the compound (1) wherein R² is a heterocyclic group-substituted carbonyl having a phenyl(lower)alkoxycarbonyl substituent on at least one nitrogen atom as described above.

In the case of the compounds of the formula (1) wherein R¹ is nitro; R² is a phenoxycarbonyl having at least one nitro substituent; R⁸ or R⁹ is a phenyl having at least one nitro substituent; R¹³ is nitro, a phenylthio-substituted lower alkoxy having at least one nitro substituent on the phenyl ring, or a phenylsulfonyl-substituted lower alkoxy having at least one nitro substituent on the phenyl ring; or R⁴ or R⁵ is a benzoyl having at least one nitro susbtituent, or a phenylsulfonyl having at least one nitro substituent on the phenyl ring, these compounds can be subjected to a reduction reaction to obtain the corresponding compounds of the formula (1) wherein R¹ is amino; R² is a phenoxycarbonyl having at least one amino substituent; R⁸ or R⁹ is a phenyl having at least one amino substituent; R¹³ is amino, or a phenylthio-substituted lower alkoxy having at least one amino substituent on the phenyl ring, or a phenylsulfonyl-substituted lower alkoxy having at least one amino substituent on the phenyl ring; or R⁴ or R⁵ is a benzoyl having at least one amino substituent, or a phenylsulfonyl having at least one amino substituent on the phenyl ring.

The reduction reaction can be carried out, for example, (1) by reducing them in an appropriate solvent with a catalytic reducing agent, or (2) by reducing them in an appropriate inert solvent with a reducing agent, such as a combination of a metal or metal salt and an acid, or a metal or metal salt and an alkali metal hydroxide, sulfide, ammonium salt, and the like.

In the case of reduction using a catalytic reducing agent (1), the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvent (e.g. N,N-dimethylformamide, etc.), and the like. The catalytic reducing agent includes, for example, palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 part by weight to 1 part by weight of the starting compound. The reaction is usually carried out at a temperature of about -20° C. to about 150° C., preferably from about 0° C. to about 100° C., under atmospheric hydrogen pressure to 10 atm., for about 0.5 to 10 hours.

In the case of the reduction (2), the reducing agent includes a combination of iron, zinc, tin or stannous chloride with a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or of iron, ferrous sulfate, zinc or tin with an alkali metal hydroxide (e.g. sodium hydroxide, etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueous ammonia, or an ammonium salt (e.g. ammonium chloride, etc.). The inert solvent includes, for example, water, acetic acid, methanol, ethanol, dioxane, and the like. The conditions of the reduction reaction are determined depending on the kinds of the reducing agent, for example, in case of a combination of stannous chloride and hydrochloric acid, it is advantageously carried out at a temperature of about 0° C. to room temperature for about 0.5 to 10 hours. The reducing agent is usually used in an amount of at least 1 mole, preferably 1 to 5 moles, to 1 mole of the starting compound.

The compound of the formula (1) wherein R¹³ is a lower alkanoyl or benzoyl can be converted into the corresponding compound (1) wherein R¹³ is a lower alkyl substituted by hydroxy and/or phenyl by reduction thereof. The reduction reaction can advantageously be carried out by using a hydrogenating reducing agent. The hydrogenating reducing agent includes, for example, lithium aluminum hydride, sodium boro hydride, diborane, and the like. The reducing agent is usually used in an amount of at least 1 mole, preferably 1 to 15 moles, to 1 mole of the starting compound. The reduction reaction is usually carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or a mixture of these solvents, at a temperature of about -60° C. to about 150° C., preferably about -30° C. to about 100° C., for about 10 minutes to about 5 hours. In case of using lithium aluminum hydride or diborane as the reducing agent, it is preferable to proceed the reaction in an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, or the like.

The compound of the formula (1) wherein R¹³ is hydroxy can be converted into the corresponding compound (1) wherein R¹³ is a group of the formula: --OR¹⁷ (wherein R¹⁷ is as defined below) by reacting it with a compound of the formula:

    R.sup.17 X

wherein R¹⁷ is a carboxy-substituted alkyl, a lower alkoxycarbonyl-substituted alkyl, a lower alkanoyloxy-substituted lower alkyl, a lower alkenyloxy-substituted lower alkyl, a lower alkoxy(lower)alkyl, an alkyl, a lower alkyl having one or two substituents selected from hydroxy, a lower alkanoyloxy, a tri(lower)alkylammonium, a lower alkoxy, or a group of the formula: ##STR62## (wherein R³² and R³³ are as defined above), a halogen-substituted lower alkyl, a lower alkylsulfonyloxy-substituted lower alkyl, a benzoyloxy-substituted lower alkyl, a tricyclo[3.3.1.1]decanyl-substituted lower alkyl, a group of the formula: ##STR63## (wherein A, l, R⁴ and R⁵ are as defined above), a carbamoyloxy-substituted lower alkyl, a lower alkylthio-substituted lower alkyl, a lower alkylsulfonyl-substituted lower alkyl, a lower alkylsulfinyl-substituted lower alkyl, an alkenyl, a lower alkanoyl, a lower alkylsulfonyl, a lower alkynyl, a phenyl(lower)alkyl, a cycloalkyl, a cycloalkenyl, a cyano-susbtituted lower alkyl, an oxilanyl-substituted lower alkyl, a phthalimido-substituted alkyl, a pyrrolyl-substituted lower alkyl, an amidino-substituted lower alkyl, a lower alkoxy(lower)alkyl having one or two substituents selected from hydroxy and an amino having optionally a lower alkyl-substituent, a morpholino-substituted lower alkyl which may optionally have a substituent selected from a lower alkyl and oxo, a benzimidazolylthio-substituted lower alkyl, a benzimidazolylsulfinyl-substituted lower alkyl, an imidazo[4,5-c]pyridylcarbonyl-substituted lower alkyl, a pyrimidylthio-substituted lower alkyl, a pyrimidylsulfinyl-substituted lower alkyl, a pyrimidylsulfonyl-substituted lower alkyl, an imidazolylthio-substituted lower alkyl which may optionally have a lower alkyl substituent on the imidazole ring, an imidazolylsulfonyl-substituted lower alkyl which may optionally have a lower alkyl substituent on the imidazole ring, a phenylthio-substituted lower alkyl which may optionally have a substituent selected from nitro and amino on the phenyl ring, a phenylsulfonyl-substituted lower alkyl which may optionally have a substituent selected from nitro and an amino having optionally one or two subsitutents selected from a lower alkanoyl and a lower alkyl on the phenyl ring, a pyridylthio-substituted lower alkyl, a pyridylsulfonyl-substituted lower alkyl having optionally an oxo substituent on the pyridine ring, and X is as defined above.

The above reaction is carried out under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8. Besides, an alkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may be added to the reaction system.

The compounds of the formula (1) wherein R¹³ is a lower alkylthio, a lower alkylthio-susbtituted lower alkoxy, a benzimidazolylthio-substituted lower alkoxy, a pyrimidylthio-substituted lower alkoxy, an imidazolylthio-substituted lower alkoxy having optionally a lower alkyl substituent on the imidazole ring, a phenylthio-substituted lower alkoxy which may optionally have a substituent selected from nitro and amino on the phenyl ring, or a pyridylthio-substituted lower alkoxy can be converted into the corresponding compounds of the formula (1) wherein R¹³ is a lower alkylsulfinyl or a lower alkylsulfonyl; or a lower alkylsulfinyl-substituted lower alkoxy or a lower alkylsulfonyl-substituted lower alkoxy; a benzimidazolylsulfinyl-substituted lower alkoxy; a pyrimidylsulfinyl-substituted lower alkoxy or a pyrimidylsulfonyl-substituted lower alkoxyl; an imidazolylsulfonyl-substituted lower alkoxy which may optionally have a lower alkyl substituent on the imidazole ring; a phenylsulfonyl-substituted lower alkoxy which may optionally have a substituent selected from nitro and amino on the phenyl ring; or pyridylsulfonyl-substituted lower alkoxy, by oxidation thereof.

The oxidation of converting the lower alkylthio into the lower alkylsulfinyl; the oxidation of converting the lower alkylsulfinyl into the lower alkylsulfonyl; the oxidation of converting the lower alkylthio-substituted lower alkoxy into the lower alkylsulfinyl-substituted lower alkoxy; the oxidation of converting the lower alkylsulfinyl-substituted lower alkoxy into the lower alkylsulfonyl-substituted lower alkoxy; the oxidation of converting the pyrimidylthio-substituted lower alkoxy into the pyridylsulfinyl-substituted lower alkoxy; and the oxiation of converting the pyrimidylsulfinyl-substituted lower alkoxy into the pyrimidylsulfonyl-substituted lower alkoxy are carried out in an appropriate solvent in the presence of an oxidizing agent. The solvent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), or a mixture of these solvents. The oxidizing agent includes, for example, peracids (e.g. performic acid, peracetic acid, trifluoro-peracetic acid, perbenzoic acid, m-chloro-perbenzoic acid, o-carboxy-perbenzoic acid, etc.), hydrogen peroxide, sodium metaperiodate, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), lead salts (e.g. lead tetraacetate, etc.), and the like. The oxidizing agent is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the starting compound. Besides, in cases of the oxidation of converting the lower alkylthio into the lower alkylsulfonyl; the oxidation of converting the lower alkylthio-substituted lower alkoxy into the lower alkylsulfonyl-substituted lower alkoxy; the oxidation of converting the pyrimidylthio-substituted lower alkoxy into the pyrimidylsulfonyl-substituted lower alkoxy; the oxidation of converting the imidazolylthio-substituted lower alkoxy having optionally a lower alkyl substituent on the imidazole ring into the imidazolylsulfonyl-substituted lower alkoxy having optionally a lower alkyl substituent on the imidazole ring; the oxiation of converting the phenylthio-substituted lower alkoxy which may optionally have a substituent selected from nitro and amino on the phenyl ring into the phenylsulfonyl-substituted lower alkoxy which may optionally have a substituent selected from nitro and amino on the phenyl ring; and the oxidation of converting the pyridylthio-substituted lower alkoxy into the pyridylsulfonyl-substituted lower alkoxy, the oxidizing agent is usually used at least 2 moles, preferably 2 to 4 moles, to 1 mole of the starting compound. The above reaction is usually carried out at a temperature of about 0° C. to about 40° C., preferably from about 0° C. to room temperature, for about 1 to 15 hours. In the above reaction, in case of the compound wherein R¹³ is a pyridylthio-substituted lower alkoxy, the pyridyl group may occasionally also be oxidized to give the corresponding pyridine N-oxide compound.

The compound of the formula (1) wherein R¹³ is a lower alkenyl, an alkenyloxy or a cycloalkenyloxy can be converted into the corresponding compound (1) wherein R¹³ is a lower alkyl, an alkoxy or a cycloalkyloxy by reduction thereof. The reduction reaction is carried out under the same conditions as in the above-mentioned reaction of converting the compound (1) wherein R⁶ or R⁷ is a phenyl(lower)alkoxycarbonyl into the compound (1) wherein R⁶ or R⁷ is hydrogen atom.

The compound of the formula (1) wherein R¹³ is a lower alkanoyl can be converted into the corresponding compound (1) wherein R¹³ is a hydroxyimino-substituted lower alkyl by reacting it with hydroxylamine. The reaction is carried out in an inert solvent in the presence or absence of a basic compound. The basic compound includes, for example, inorganic basic compounds (e.g. sodium hydroxide, potassium hyroxide, sodium carbonate, potassium carbonate, etc.), lower alkanic acid alkali metal salts (e.g. sodium acetate, etc.), organic bases (e.g. piperidine, pyridine, 4-dimethylaminopyridine, triethylamine, DBN, DBU, DABCO, etc.), and the like. The solvent includes any solvent which does not affect on the reaction, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), fatty acids (e.g. acetic acid, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, ethylene glycol monomethyl ether, etc.), aromatic hyrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), aprotic polar solvents (e.g. dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The hydroxylamine is usually used in an amount of at least 1 mole, preferably 1 to 5 moles, to 1 mole of the starting compound. The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 1 to 15 hours.

In case of the compounds of the formula (1) wherein R¹³ is a lower alkoxycarbonyl-substituted alkoxy, a lower alkanoyloxy-substituted lower alkoxy, a lower alkanoyloxy-substituted lower alkyl, a lower alkanoyloxy, a lower alkoxycarbonyl, a lower alkoxycarbonyl(lower)alkyl, R⁶ or R⁷ is a lower alkoxycarbonyl(lower)alkyl, R⁴ or R⁵ is a lower alkanoyloxy(lower)alkanoyl, a cycloalkylcarbonyl having at least one substituent of a lower alkanoyloxy on the cycloalkyl group, or a lower alkanoyloxy(lower)alkyl, or R¹ is a lower alkanoyloxy, these compounds can be converted by hydrolysis thereof into the corresponding compounds (1) wherein R¹³ is a carboxy-substituted lower alkoxy, a hydroxy-substituted lower alkoxy, a hydroxy-substituted lower alkyl, hydroxy, carboxy, a carboxy-substituted lower alkyl, R⁶ or R⁷ is a carboxy-substituted lower alkyl, R⁴ or R⁵ is a hydroxy-substituted lower alkanoyl, a cycloalkylcarbonyl having at least one hydroxy substituent on the cycloalkyl group, or a hydroxy-substituted lower alkyl, or R¹ is hydroxy. The above hydrolysis can be carried out under the same conditions as in the hydrolysis of the compound (1) where R⁴ or R⁵ is a lower alkoxycarbonyl to convert into a compound (1) where R⁴ or R⁵ is hydrogen atom as described herebefore.

In the case of the compounds of the formula (1) wherein R¹ is a lower alkanoyl-substituted amino; R² is a an alkanoyl; R² is a group of the formula: ##STR64## (wherein R¹³ and p are as defined above), or a phenoxycarbonyl having at least one lower alkanoyl-substituted amino on the phenyl ring; R⁴ or R⁵ is a lower alkanoyl having optionally one to three substituents of a halogen atom, an amino-substituted lower alkanoyl having a lower alkanoyl substituent, an amino-substituted lower alkyl having a lower alkanoyl substituent, a piperidinylcarbonyl having a lower alkanoyl substituent on the nitrogen atom of the piperidine ring, or a phenylsulfonyl having at least one lower alkanoyl-substituted amino on the phenyl ring; R⁶ or R⁷ is a lower alkaonyl having one to three substituents of a halogen atom; or R⁴ and R⁵ or R¹¹ and R¹² form a heterocyclic group which has a lower alkanoyl substituent on the nitrogen atom of said heterocyclic group, these compounds can be converted by hydrolysis into the corresponding compounds of the formula (1) wherein R¹ is amino; R² is hydrogen atom; R² is a phenoxycarbonyl having at least one amino substituent on the phenyl ring; R⁴ or R⁵ is hydrogen atom, an amino-substituted lower alkanoyl, an amino-substituted lower alkyl, unsubstituted piperidinylcarbonyl, or a phenylsulfonyl having at least one amino substituent on the phenyl group; R⁶ or R⁷ is hydrogen atom; or R⁴ and R⁵ or R¹¹ and R¹² form a heterocyclic group which have no substituent on the nitrogen atom of said heterocyclic group. The hydrolysis can be carried out under the same conditions as in the hydrolysis of the compound (1) where R⁴ or R⁵ is a lower alkoxycarbonyl to convert into a compound (1) where R⁴ or R⁵ is hydrogen atom as described hereinbefore.

In the case of the compounds of the formula (1) wherein R⁴ or R⁵ is a phenyl(lower)alkyl; R¹¹ or R¹² is a phenyl(lower)alkyl; or R⁴ and R⁵ or R¹¹ and R¹² form a heterocyclic group which has a phenyl(lower)alkyl substituent on the nitrogen atom of said heterocyclic group, these compounds can be subjected to a reduction reaction to obtain the corresponding compounds of the formula (1) wherein R⁴ or R⁵ is hydrogen atom; R¹¹ or R¹² is hydrogen atom; or R⁴ and R⁵ or R¹¹ and R¹² form a heterocyclic group which has no substituent on the nitrogen atom of said heterocyclic group. The reduction is carried out under the same conditions as in the above-mentioned reduction of converting a compound (1) wherein R⁶ or R⁷ is a phenyl(lower)alkoxycarbonyl into the compound (1) wherein R⁶ or R⁷ is hydrogen atom. Besides, the reduction reaction can also be carried out by using the same solvent and catalyst as in the catalytic hydrogenation reaction together with a hydrogen donor (e.g. formic acid, cyclohexene, hydrazine hydrate, ammonium formate, etc.), at a temperature of from room temperature to 150° C., preferably from room temperature to 100° C., for about 1 to 6 hours.

The compound of the formula (1) wherein R² is a benzoyl having at least one lower alkenyloxy substituent can be converted into the corresponding compound (1) wherein R² has at least two substituents of hydroxy and a lower alkenyl by subjecting it to Claisen rearrangement. The reaction is carried out by heating said compound in an appropriate solvent. The solvent includes solvents having a high boiling point, such as dimethylformamide, diphenyl ether, dimethylaniline, tetrahydronaphthalene, etc. The reaction is usually carried out at a temperature of 100° C. to 250° C., preferably from 150° C. to 250° C. for about 1 to 30 hours.

In the case of the compounds of the formula (1) wherein R¹³ is a carboxy-substituted alkoxy, carboxy or a carboxy-substituted lower alkyl; R⁶ or R⁷ is a carboxy-substituted lower alkyl; R⁴ and R⁵ form a heterocyclic group which has at least one carboxyl substituent on the heterocyclic group, these compounds can be converted by esterification thereof into the corresponding compounds of the formula (1) wherein R¹³ is a lower alkoxycarbonyl-substituted alkoxy, a lower alkoxycarbonyl, or a lower alkoxycarbonyl(lower)alkyl; R⁶ or R⁷ is a lower alkoxycarbonyl(lower)alkyl; or R⁴ and R⁵ form a heterocyclic group which has at least one lower alkoxycarbonyl substituent on the heterocyclic group. The esterification is usually carried out by reacting the compound with an alochol (e.g. methanol, ethanol, isopropanol, etc.) in the presence of a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.) and a halogenating agent (e.g. thionyl chloride, phosphorus oxychloride, phosphorus pentoxide, phosphorus trichloride, etc.), at a temperature of 0° C. to about 150° C., preferably from 50° C. to 100° C., for about 1 to 10 hours.

In the case of the compounds of the formula (1) wherein R⁴ or R⁵ is a lower alkoxycarbonyl or a lower alkoxycarbonyl(lower)alkyl; R⁶ or R⁷ is a lower alkoxycarbonyl(lower)alkyl or a carboxy(lower)alkyl; or R⁴ and R⁵ form a heterocyclic group which has at least one substituent of carboxy or a lower alkoxycabonyl on the heterocyclic group, these compounds can be reacted with an amine having optionally a lower alkyl-substituent or an amine having optionally a substituent selected from a lower alkyl and a lower alkanoyl under the same coniditons as in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5 to obtain the corresponding compounds (1) wherein R⁴ or R⁵ is an amido having optionally a lower alkyl substituent, or an amido-substituted lower alkyl which has optionally a substituent selected from a lower alkyl and a lower alkanoyl; R⁶ or R⁷ is an amido-substituted lower alkyl having optionally a lower alkyl substituent on the amido group; or R⁴ and R⁵ form a heterocyclic group being substituted by at least one amido group which has optionally a lower alkyl substituent. In this reaction, when the R⁶ in the compound (1) is hydrogen atom and the R⁷ is a carboxy(lower)alkyl, these groups may occasionally form an intermolecular amido bond to give the compound wherein R⁶ and R⁷ form a group of the formula: ##STR65## (wherein A is as defined above).

In case of the compounds of the formula (1) wherein R⁴ or R⁵ is a benzoyl which has at least one amino having optionally one lower alkyl substituent; a phenylsulfonyl which phenyl ring is substituted by at least one amino having optionally one lower alkyl substituent; an amino-substituted lower alkyl wherein the amino group may optionally have one lower alkyl substituent; or R¹³ is a phenylsulfonyl-substituted lower alkoxy which phenyl ring is substituted by at least one amino having optionally one lower alkyl substituent, these compounds can be converted into the corresponding compounds (1) wherein R⁴ or R⁵ is a benzoyl which has at least one amino having one or two lower alkyl substituents; a phenylsulfonyl which phenyl ring is substituted by at least one amino having one or two lower alkyl substituents; an amino-substituted lower alkyl wherein the amino group has one or two lower alkyl substituents; or R¹³ is a phenylsulfonyl-substituted lower alkoxy which phenyl ring is substituted by at least one amino having one or two lower alkyl substituents by treating them under the same conditions as in the reaction of the compound (1k) and the compound (14) in the above Reaction Scheme-9A.

In case of the compounds of the formula (1) wherein R⁴ or R⁵ is a benzoyl which has at least one amino having optionally one lower alkyl substituent; a phenylsulfonyl which phenyl ring is substituted by at least one amino having optionally one lower alkyl substituent; an amino-substituted lower alkyl wherein the amino group may optionally have one lower alkyl substituent; or R¹³ is a phenylsulfonyl-substituted lower alkoxy which phenyl ring is substituted by at least one amino having optionally one lower alkyl substituent, these compounds can be converted into the corresponding compounds (1) wherein R⁴ or R⁵ is a benzoyl which has a substituent selected from a lower alkanoyl and a lower alkoxycarbonyl and further at least one amino having optionally one lower alkyl substituent; a phenylsulfonyl which phenyl ring is substituted by a lower alkanoyl and further by at least one amino having optionally one lower alkyl substituent; an amino-substituted lower alkyl wherein the amino group has a lower alkanoyl substituent and further at least one amino having optionally a lower alkyl substituent; or R¹³ is a phenylsulfonyl-substituted lower alkoxy which phenyl ring is substituted by a lower alkanoyl and further by at least one amino having optionally one lower alkyl substituent by treating them under the same conditions as in the reaction of the compound (1k) and the compound (15) in the above Reaction Scheme-9A.

The compound of the formula (1d) can also be prepared by reducing the compound (1) wherein R² is a phenyl(lower)alkyl under the same conditions as in the above-mentioned reduction of the compound (1) wherein R² is a heterocyclic group-substituted carbonyl which has at least one phenyl(lower)alkoxycarbonyl on the nitrogen atom. The reduction reaction may be carried out in the presence of an acid (e.g. hydrochloric acid, etc.).

The compound (1) wherein R¹³ is a tri(lower)alkylammonium can also be prepared by reacting a compound (1) wherein R¹³ is a di(lower)alkylamino with a compound of the formula: R⁵⁰ X (wherein R⁵⁰ is a lower alkyl and X is a halogen atom) under the same conditions as in the reaction of the compound (1h) and the compound (11) in the above Reaction Scheme-8.

The compound (1) wherein R¹³ is an ammonium(lower)alkoxy having three substituents selected from a lower alkyl, a lower alkenyl and oxo can also be prepared by reacting a compound (1) wherein R¹³ is an amino-substituted lower alkoxy which has two substituents selected from a lower alkyl and/or a lower alkenyl on the amino group with a compound of the formula: R⁵¹ X (wherein R⁵¹ is a lower alkyl or a lower alkenyl, and X is as defined above) under the same conditions as in the reaction of the compound (1h) and the compound (11) of the above Reaction Scheme-8. Besides, said compound can be converted into a compound (1) wherein R¹³ is an ammonium(lower)alkoxy having oxo substituent by oxidizing the compound under the same conditions as in the above-mentioned oxidization reaction for converting the compound (1) wherein R¹³ is a lower alkylthio into the corresponding compound (1) wherein R¹³ is a lower alkylsulfonyl.

Among the active compounds (1) of this invention, the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc., alkali metal carbonates or hydrogen carbonates such as sodium carbonate, sodium hydrogen carbonate, etc., alkali metal alcoholates such as sodium methylate, potassium ethylate, etc. Besides, among the active compounds (1) of this invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc., and organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, citric acid, succinic acid, benzoic acid, etc. Among the active compounds (1) of the invention, the compounds having an ammonium group can be converted into a salt thereof with a pharmaceutically acceptable halogen anion (e.g. chlorine anion, bromine anion, fluorine anion, or iodine anion). These salts are useful as an active ingredient as like as the compounds (1) in the free form.

In addition, the compounds (1) of this invention include stereoisomers and optical isomers, and these isomers are also useful as the active ingredient in this invention.

The compounds of this invention thus obtained can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromtography, preparative thin layer chromatography, extraction with a solvent, and the like.

The compounds and their salts of this invention are useful as a vasopressin antagonist and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional dilutents or carriers such as fillers, thickening agents, binders, wetting agents, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations may be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodium arginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin, starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers include vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the compound of this invention with the above carriers into hard gelatin capsules or soft capsules in a usual manner. In the preparation of injections, the solutions, emulsions or suspendions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, aqueous lactic acid solution, ethyl alcohol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required.

The amount of the active compound of this invention (active ingredient) to be incorporated into the anti-vasopressin preparations is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70% by weight, more preferably 5 to 50% by weight.

The anti-vasopressin preparation of this invention may be administered in any method, and suitable method for administration may be determined in accordance with various forms of preparation, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For instance, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intraveneously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.

The dosage of the anti-vasopressin agent of this invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but is usually in the range of about 0.6 to 50 mg of the active compound of this invention per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of 10 to 1000 mg per the dosage unit.

EXAMPLES

The present invention is illustrated by the following Preparations of anti-vasopressin agent, Reference Examples of processes for preparing the starting compounds to be used for preparing the active compounds, Examples of processes for preparing the active compounds, and Experiments of the activities of the active compounds of this invention.

Preparation 1

Film coated tablets are prepared from the following components.

    ______________________________________     Components              Amount     ______________________________________     1-[1-(4-Dimethylaminobenzoyl)-4-                             150 g     piperidinyl]-3,4-dihydrocarbostyril     Avicel                  40 g     (tradename of microcrystalline cellulose,     manufactured by Asahi Chemical Industry Co.,     Ltd., Japan)     Corn starch             30 g     Magnesium stearate       2 g     Hydroxypropyl methylcellulose                             10 g     Polyethylene glycol-6000                              3 g     Castor oil              40 g     Ethanol                 40 g     ______________________________________

The active component of this invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets.

Preparation 2

Tablets are prepared from the following components.

    ______________________________________     Components            Amount     ______________________________________     1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-                            150 g     piperidinyl]-3,4-dihydrocarbostyril     Citric acid            1.0 g     Lactose               33.5 g     Dicalcium phosphate   70.0 g     Pullonic F-68         30.0 g     Sodium laurylsulfate  15.0 g     Polyvinylpyrrolidone  15.0 g     Polyethylene glycol (Carbowax 1500)                            4.5 g     Polyethylene glycol (Carbowax 6000)                           45.0 g     Corn starch           30.0 g     Dry sodium stearate    3.0 g     Dry magnesium stearate                            3.0 g     Ethanol               q.s.     ______________________________________

The active compound of this invention, citric acid, lactose, dicalcium phosphate, Pullonic F-68 and sodium laurylstearate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100° C. for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape.

The core tablets thus prepared are vanished and dusted with talc in order to guard from wetting. Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. In order to give round shape and smooth surface to the tablets, further undercoating and coating with lubricant are applied thereto. The tablets are further coated with a coloring coating material until the desired colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gloss.

Preparation 3

An injection preparation is prepared from the following components.

    ______________________________________     Components                Amount     ______________________________________     7-Fluoro-1-[1-(2,4-dimethoxybenzoyl)-4-                               5      g     piperidinyl]-3,4-dihydrocarbostyril     Polyethylene glycol (molecular weight: 4000)                               0.3    g     Sodium chloride           0.9    g     Polyoxyethylene sorbitan monooleate                               0.4    g     Sodium metabisulfite      0.1    g     Methyl-paraben            0.18   g     Propyl-paraben            0.02   g     Distilled water for injection                               10.0   ml     ______________________________________

The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of half volume of the above with stirring at 80° C. The solution thus obtained is cooled to 40° C., and the active compound of this invention and further polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation.

Reference Example 1

A mixture of aniline (28.0 g), 1-benzyl-4-piperidone (56.7 g), acetic acid (55 ml), platinum oxide (0.9 g) and ethanol (420 ml) is subjected to catalytic reduction at room temperature at normal pressure for 2 hours. The catalyst is removed by filtration and the filtrate is concentrated.

The resulting residue is made alkaline with a 10% aqueous sodium hydroxide solution and extracted with dichloromethane. After the extract is dried and concentrated, n-hexane is added to the residue and the formed crystals are separated by filtration and recrystallized from n-hexane to give N-(1-benzyl-4-piperidinyl)aniline (63.3 g) as colorless prisms, m.p. 73°-75° C.

Using appropriate starting materials, the same procedure as in Reference Example 1 is repeated to give the following compounds:

N-(1-Benzyl-4-piperidinyl)-4-methoxyaniline, m.p. 75°-76° C. (recrystallized from n-hexane), colorless prisms

N-(1-Benzyl-4-piperidinyl)-4-methylaniline, m.p. 95°-96° C. (recrystallized from n-hexane), colorless prisms

N-(1-Benzyl-4-piperidinyl)-4-fluoroaniline, m.p. 87°-88° C. (recrystallized from n-hexane), colorless prisms

N-(1-Benzyl-4-piperidinyl)-3-methylaniline

NMR (CDCl₃) δ: 1.38-1.64 (2H, m), 2.00-2.20 (4H, m), 2.26 (3H, s), 2.72-2.94 (2H, m), 3.20-3.40 (1H, m), 3.62 (2H, s), 3.55-3.70 (1H, m), 6.39 (2H, d, J=6.2 Hz), 6.49 (1H, d, J=7.4 Hz), 7.04 (1H, t, J=7.4 Hz), 7.20-7.45 (6H, m)

N-(1-Benzyl-4-piperidinyl)-3-fluoroaniline, m.p. 72°-74° C. (recrystallized from n-hexane), colorless prisms

N-(1-Benzyl-4-piperidinyl)-2-methylaniline, m.p. 100°-102° C. (recrystallized from n-hexane), colorless prisms

N-(1-Benzyl-4-piperidinyl)-3-acetaminoaniline

NMR (CDCl₃) δ: 1.34-2.73 (2H, m), 1.82-2.25 (7H, m), 2.68-2.95 (2H, m), 3.28 (1H, brs), 3.51 (2H, s), 3.58-3.80 (1H, m), 6.30-6.60 (2H, m), 7.01-7.53 (7H, m)

N-(1-Benzoyl-4-piperidinyl)aniline, m.p. 161°-163° C. (recrystallized from ethanol), white powders

N-(1-Benzyl-3-piperidinyl)aniline

NMR (CDCl₃) δ: 1.4-1.8 (4H, m), 2.3-2.5 (3H, m), 2.7-2.8 (1H, m), 3.51 (2H, d, J=2.4 Hz), 3.4-3.7 (1H, m), 3.9-4.1 (1H, m), 6.6-6.8 (3H, m), 7.1-7.3 (7H, m)

N-(1-Benzyl-3-pyrrolidinyl)aniline

NMR (CDCl₃) δ: 1.6-1.8 (1H, m), 2.2-2.6 (3H, m), 2.7-2.9 (2H, m), 3.62 (2H, s), 3.8-4.2 (1H, m), 6.5-6.8 (3H, m), 7.1-7.4 (7H, m)

N-(1-Benzyl-3-methyl-4-piperidinyl)aniline

NMR (CDCl₃) δ: 0.9-1.1 (3H, m), 1.6-2.0 (2H, m), 2.0-2.7 (4H, m), 2.8-3.0 (1H, m), 3.3-3.7 (3H, m), 6.5-6.7 (3H, m), 7.1-7.4 (7H, m)

Reference Example 2

To a mixture of N-(1-benzyl-4-piperidinyl)aniline (0.9 g), diisopropyl ether (30 ml) and triethylamine (0.5 g) is added β-ethoxyacrylic acid chloride (0.7 g) in portions at 60° C. After refluxing for 1 hour, the reaction mixture is poured into ice-water and extracted with ethyl acetate. The extract is dried and concentrated and to the resulting residue is added n-hexane and the formed crystals are separated by filtration and recrystallized from n-hexane to give N-(β-ethoxyacryloyl)-N-(1-benzyl-4-piperidinyl)aniline (1.1 g) as white powders, m.p. 106°-108° C.

Reference Example 3

To a mixture of N-(1-benzyl-4-piperidinyl)aniline (1.8 g), diisopropyl ether (20 ml) and triethylamine (0.87 g) is added dropwise a solution of β-n-butoxyacrylic acid chloride (1.4 g) in diisopropyl ether (5 ml) with stirring and heating at 70° C. After completion of dropwise addition, the mixture is further stirred with heating at the same temperature for 0.5 hour. After cooling, water is added to the reaction mixture and the mixture is subjected to extraction with ethyl acetate. The extract is washed with water and dried over magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography give N-(β-n-butoxyacryloyl)-N-(1-benzyl-4-piperidinyl)aniline (2.6 g).

NMR (CDCl₃) δ: 0.86 (3H, t, J=7.1 Hz), 1.2-1.4 (1H, m), 1.4-1.6 (2H, m), 1.6-1.9 (2H, m), 2.1-2.3 (1H, m), 2.4-2.6 (3H, m), 2.7-2.9 (1H, m), 3.4-3.7 (4H, m), 4.86 (1H, d, J=12 Hz), 5.1-5.3 (1H, m), 7.1-7.5 (10H, m), 7.47 (1H, d, J=12 Hz)

Using appropriate starting materials, the procedure of the above Reference Examples 2 and 3 is repeated to give the following compounds:

N-(β-n-Butoxyacryloyl)-N-(1-benzyl-3-piperidinyl)aniline

NMR (CDCl₃) δ: 0.85 (3H, t, J=7 Hz), 0.8-2.0 (10H, m), 2.6-2.8 (1H, m), 3.0-3.2 (1H, m), 3.40, 3.53 (2H, AB-q, J=13.2 Hz), 3.62 (2H, t, J=6.3 Hz), 4.7-5.0 (2H, m), 7.0-7.6 (10H, m)

N-(β-n-Butoxyacryloyl)-N-(4-nitrophenyl)aniline

NMR (CDCl₃) δ: 0.90 (3H, t, J=7.2 Hz), 1.3-1.6 (2H, m), 1.6-1.8 (2H, m), 3.76 (2H, t, J=6.4 Hz), 5.17 (1H, d, J=11.9 Hz), 7.1-7.6 (7H, m), 7.66 (1H, d, J=11.9 Hz), 8.14 (2H, d, J=9.2 Hz)

Reference Example 4

2-(2-Carbamoylethyl)aniline (37 g) and 1-benzoyl-4-oxopiperidine (67.6 g) are dissolved in ethanol (500 ml) and to the solution is added acetic acid to adjust the pH of the solution to about 5.5. To the solution is further added PtO₂ (1 g) and the mixture is stirred under 1 atm. at room temperature under H₂ atmosphere. When H₂ is absorbed up to 5 liters, the reaction is stopped and the catalyst is separated by filtration. The filtrate is concentrated to give N-(1-benzoyl-4-piperidinyl)-2-(2-carbamoylethyl)aniline.

Reference Example 5

To a concentrated sulfuric acid (15 ml) is added in portions N-(β-ethoxyacryloyl)-N-(1-benzyl-4-piperidinyl)aniline (1.1 g) at 60° C. After stirring the mixture at the same temperature for 15 minutes, the reaction mixture is poured into ice-water, made alkaline with a 10% aqueous sodium hydroxide solution and extracted with dichloromethane. After the extract is concentrated by distilling off the solvent, the resulting residue is purified by silica gel column chromatography (eluent; dichloromethane:methanol=50:1) and recrystallized from ethyl acetate to give 1-(1-benzyl-4-piperidinyl)carbostyril (0.8 g) as white powders, m.p. 97°-99° C.

Using appropriate starting materials, the procedure of Reference Example 5 is repeated to give the following compounds:

6-Methoxy-1-(1-benzyl-4-piperidinyl)carbostyril hydrochloride as white powders, m.p. 227°-230° C. (recrystallized from methanol)

6-Methyl-1-(1-benzyl-4-piperidinyl)carbostyril hydrochloride as white powders, m.p. 259°-261° C. (recrystallized from ethanol)

6-Fluoro-1-(1-benzyl-4-piperidinyl)carbostyril hydrochloride as white powders, m.p. 232°-236° C. (recrystallized from ethanol)

7-Methyl-1-(1-benzyl-4-piperidinyl)carbostyril

NMR (CDCl₃) δ: 1.62-1.85 (2H, m), 2.18-2.40 (2H, m), 2.52 (3H, s), 2.75-3.22 (4H, m), 3.61 (2H, s), 5.28 (1H, brs), 6.58 (1H, d, J=9.3 Hz), 7.01 (1H, d, J=7.9 Hz), 7.20-7.48 (6H, m), 7.55 (1H, d, J=9.3 Hz)

7-Fluoro-1-(1-benzyl-4-piperidinyl)carbostyril hydrochloride as white powders, m.p. 254°-257° C. (recrystallized from ethanol)

8-Methyl-1-(1-benzyl-4-piperidinyl)carbostyril hydrochloride as white powders, m.p. 253°-257° C. (recrystallized from ethanol)

7-Acetamido-1-(1-benzyl-4-piperidinyl)carbostyril

NMR (CDCl₃) δ: 1.60-1.82 (2H, m), 2.11-2.35 (2H, m), 2.24 (3H, s), 2.72-3.15 (4H, m), 3.55 (2H, s), 5.25 (1H, bs), 6.54 (1H, d, J=8.7 Hz), 7.14-7.60 (9H, m), 8.28 (1H, s), 8.63 (1H, s)

1-(1-Benzyl-3-pyrrolidinyl)carbostyril

NMR (CDCl₃) δ: 2.1-2.7 (4H, m), 3.1-3.2 (1H, m), 3.2-3.4 (1H, m), 3.59 (1H, d, J=12.9 Hz), 3.87 (1H, d, J=12.9 Hz), 6.4-6.5 (1H, m), 6.64 (1H, d, J=9.4 Hz), 7.1-7.7 (9H, m), 8.74 (1H, d, J=8.6 Hz)

1-(1-Benzyl-3-methyl-4-piperidinyl)carbostyril

NMR (CDCl₃) δ: 1.30 (3H, d, J=7.1 Hz), 1.7-1.8 (1H, m), 2.0-2.2 (1H, m), 2.3-2.5 (2H, m), 2.8-2.9 (1H, m), 3.0-3.2 (1H, m), 3.48 (1H, d, J=13.5 Hz), 3.62 (1H, d, J=13.5 Hz), 3.6-3.9 (1H, m), 4.4-4.6 (1H, m), 6.58 (2H, d, J=9.4 Hz), 7.56 (2H, d, J=9.4 Hz), 7.1-7.6 (9H, m)

1-(1-Benzyl-4-piperidinyl)-7-dimethylaminocarbostyril

NMR (CDCl₃) δ: 1.65-1.82 (2H, m), 2.18-2.40 (2H, m), 2.80-3.20 (4H, m), 3.12 (6H, s), 3.61 (2H, s), 5.28 (1H, brs), 6.35 (1H, d, J=9.2 Hz), 6.65 (1H, dd, J=8.8 Hz, 2.2 Hz), 6.80-7.10 (1H, m), 7.15-7.40 (6H, m), 7.48 (1H, d, J=9.2 Hz)

1-(4-Nitrophenyl)carbostyril

NMR (CDCl₃) δ: 6.60 (1H, d, J=8.3 Hz), 6.78 (1H, d, J=9.6 Hz), 7.2-7.4 (2H, m), 7.52 (2H, d, J=9.0 Hz), 7.64 (1H, dd, J=1.5 Hz, 6.1 Hz), 7.83 (1H, d, J=9.6 Hz), 8.48 (2H, d, J=9.0 Hz)

Reference Example 6

To N-(1-benzyl-4-piperidinyl)aniline (13.3 g) is added benzene (70 ml) and thereto is added dropwise a solution of diketene (5.0 g) in benzene (10 ml) at room temperature. After refluxing for 1 hour, the reaction mixture is concentrated by distilling off the solvent. To the resulting residue are added ethyl acetate and diethyl ether and the formed crystals are separated by filtration and recrystallized from ethyl acetate/n-hexane to give N-(1-benzyl-4-piperidinyl)-α-acetoacetoanilide (16.0 g) as white powders, m.p. 124°-126° C.

Reference Example 7

N-(1-Benzyl-4-piperidinyl)-α-acetoacetoanilide (13.2 g) is added in portions to concentrated sulfuric acid (80 ml) at 80° C. After stirring at 90° C. for 1 hour, the reaction mixture is poured into ice-water, made alkaline with potassium carbonate and then extracted with ethyl acetate. After the extract is concentrated by distilling off the solvent, the resulting residue is purified by silica gel column chromatography (eluent; ethyl acetate:methanol=100:1) to give 4-methyl-1-(1-benzyl-4-piperidinyl)carbostyril (1.5 g).

NMR (CDCl₃) δ: 1.60-1.85 (2H, m), 2.15-2.35 (2H, m), 2.42 (3H, s), 2.65-3.20 (4H, m), 3.59 (2H, s), 5.29 (1H, brs), 7.13-7.95 (9H, m)

Reference Example 8

To 1-(1-benzyl-4-piperidinyl)-7-acetylaminocarbostyril (3.0 g) are added ethanol (32 ml) and an aqueous 10% sodium hydroxide solution (32 ml) and the mixture is refluxed for 1 hour. After the reaction mixture is concentrated by distilling off the solvent, water is added to the residue and the resulting solution is extracted with dichloromethane. The extract is concentrated by distilling off the solvent and recrystallized from ethanol/chloroform to give 1-(1-benzyl-4-piperidinyl)-7-aminocarbostyril (2.4 g) as white powders, m.p. 238°-241° C.

Reference Example 9

To a mixture of 1-(1-benzyl-4-piperidinyl)-7-aminocarbostyril (0.7 g), methanol (10 ml) and 37% formalin (1.4 ml) is added NaBH₃ CN (0.3 g) in portions. Thereafter, acetic acid (0.7 ml) is added thereto in portions at room temperature and the mixture is stirred at the same temperature for 1 hour. After completion of the reaction, water is added to the reaction mixture and the mixture is neutralized with an aqueous potassium carbonate and then extracted with ethyl acetate. The extract is concentrated by distilling off the solvent to give 1-(1-benzyl-4-piperidinyl)-7-dimethylaminocarbostyril (0.7 g).

NMR (CDCl₃) δ: 1.65-1.82 (2H, m), 2.18-2.40 (2H, m), 2.80-3.20 (4H, m), 3.12 (6H, s), 3.61 (2H, s), 5.28 (1H, brs), 6.35 (1H, d, J=9.2 Hz), 6.65 (1H, dd, J=8.8 Hz, 2.2 Hz), 6.80-7.10 (1H, m), 7.15-7.40 (6H, m), 7.48 (1H, d, J=9.2 Hz)

Reference Example 10

To 10% Pd--C (0.1 g) is added acetic acid (20 ml) and then 1-(4-nitrophenyl)carbostyril (0.9 g) and the mixture is subjected to catalytic reduction at 80° C. under normal pressure. After completion of the reaction, 10% Pd--C is removed by filtration and the resulting solution is concentrated under reduced pressure. To the concentrate is added water and the solution is made alkaline with an aqueous sodium hydroxide solution and then extracted with dichloromethane. The extract is washed with water and dried over magnesium sulfate. The solvent is distilled off under reduced pressure and the residue is purified by silica gel column chromatography and recrystallized from ethanol to give 1-(4-aminophenyl)carbostyril (0.66 g) as brown powders, m.p. 225°-230° C.

NMR (CDCl₃) δ: 2.7-2.9 (2H, m), 3.0-3.1 (2H, m), 3.8 (2H, brs), 6.50 (1H, dd, J=1.4 Hz, 7.8 Hz), 6.7-6.8 (2H, m), 6.8-7.1 (4H, m), 7.1-7.2 (1H, m)

Reference Example 11

To a solution of 3,4-dihydrocarbostyril (3 g) in N-methylpyrrolidone (30 ml) are added p-iodobenzoic acid (5.58 g), copper (0.3 g) and potassium carbonate (3.03 g) and the mixture is stirred at 150° C. for 4 hours. An aqueous sodium hydroxide solution is added to the reaction mixture and the mixture is washed with dichloromethane. The aqueous layer is made acidic with concentrated hydrochloric acid and then extracted with diethyl ether and the extract is dried over magnesium sulfate. After the solvent is distilled off under reduced pressure, methanol (50 ml) is added to the residue and thionyl chloride (10 ml) is slowly while to the solution while stirring with ice-cooling. After completion of dropwise addition, the mixture is refluxed for 0.5 hour. After methanol is distilled off under reduced pressure, water is added to the residue and the solution is extracted with dichloromethane and dried over magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography to give 1-(4-methoxycarbonylphenyl)-3,4-dihydrocarbostyril (1.44 g).

NMR (CDCl₃) δ: 2.7-2.9 (2H, m), 3.0-3.2 (2H, m), 3.93 (3H, s), 6.3-6.4 (1H, m), 6.9-7.1 (2H, m), 7.2-7.3 (1H, m), 7.34 (2H, d, J=8.6 Hz), 8.17 (2H, d, J=8.6 Hz)

Reference Example 12

To a solution of 1-(4-methoxycarbonylphenyl)-3,4-dihydrocarbostyril (1.84 g) in methanol (40 ml) is added a 5% aqueous sodium hydroxide solution (20 ml) and the mixture is stirred at room temperature overnight. Methanol is distilled off under reduced pressure and to the residue is added water. After the solution is washed with dichloromethane, the aqueous layer is made acidic with concentrated hydrochloric acid and extracted with diethyl ether and dried over magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography, followed by recrystallization from ethanol to give 1-(4-carboxyphenyl)-3,4-dihydrocarbostyril (0.87 g) as pale yellow powders, m.p. 265°-270° C.

NMR (DMSO-d₆) δ: 2.7-2.9 (2H, m), 2.9-3.2 (2H, m), 6.21 (1H, d, J=7.4 Hz), 6.9-7.2 (2H, m), 7.29 (1H, d, J=6.3 Hz), 7.38 (2H, d, J=8.3 Hz), 8.08 (2H, d, J=8.3 Hz)

Reference Example 13

Using appropriate starting materials, the procedure of Reference Example 1 is repeated to give the following compounds:

N-(1-Benzyl-4-piperidinyl)-3,4-difluoroaniline

NMR (CDCl₃) δ: 1.30-1.65 (2H, m), 1.86-2.25 (4H, m), 2.72-2.97 (2H, m), 3.04-3.30 (1H, m), 3.36-3.60 (3H, m), 6.11-6.46 (2H, m), 6.80-7.00 (1H, m), 7.30 (5H, s)

N-(1-Benzyl-4-piperidinyl)-3,5-difluoroaniline

NMR (CDCl₃) δ: 1.45-1.62 (2H, m), 1.95-2.25 (4H, m), 2.75-2.93 (2H, m), 3.10-3.30 (1H, m), 3.52 (2H, s), 3.70-3.87 (1H, m), 5.98-6.15 (3H, m), 7.20-7.48 (5H, m)

Reference Example 14

Using appropriate starting materials, the procedure of Reference Example 5 is repeated to give the following compounds:

6,7-Difluoro-1-(1-benzyl-4-piperidinyl)carbostyril as white powders (recrystallized from ethanol), m.p. 132°-134° C.

5,7-Difluoro-1-(1-benzyl-4-piperidinyl)carbostyril as colorless prisms (recrystallized from ethanol), m.p. 165°-166° C.

Reference Example 15

To a mixture of N-(1-benzyl-4-piperidinyl)aniline (6.4 g), diisopropyl ether (70 ml) and triethylamine (4.8 ml) is added at 70° C. a solution of α-methylcinnamoyl chloride (4.9 g) in diisopropyl ether (10 ml). After stirring at the same temperature for 30 minutes, water is added to the reaction solution and the mixture is extracted with ethyl acetate. The extract is concentrated by distilling off the solvent and to the resulting residue is added diethyl ether and the formed crystals are separated by filtration to give N-(α-methylcinnamoyl)-N-(1-benzyl-4-piperidinyl)aniline (8.9 g), m.p. 150°-152° C.

Reference Example 16

To grinded aluminum chloride (26 g) are added chlorobenzene (26 ml) and N-(α-methylcinnamoyl)-N-(1-benzyl-4-piperidinyl)aniline (8.7 g) and the mixture is heated at 110° C. for 1 hour. After cooling, the reaction mixture is poured into ice-water and made alkaline with an aqueous sodium hydroxide solution. After extraction with dichloromethane, the extract is concentrated and the resulting residue is purified by silica gel column chromatography (eluent; methylene chloride). The purified substance is converted into hydrochloride and then recrystallized from ethanol/water to give 1-(1-benzyl-4-piperidinyl)-3-methylcarbostyril hydrochloride (5.8 g) as colorless needles, m.p. 274°-276° C.

Reference Example 17

A mixture of o-aminobenzyl alcohol (20.4 g), ethanol (300 ml), 1-benzyl-4-piperidone (31.6 g) and acetic acid (40 ml) is refluxed for 30 minutes. After concentrating the reaction mixture, water is added to the resulting residue and the mixture is extracted with dichloromethane. After concentrating the extract to remove the solvent, n-hexane is added to the resulting residue and the formed crystals are separated by filtration to give 1-benzylspiro[piperidin-4,2'-(4H-1',2'-dihydro-3,1-benzoxadine)] (37.7 g), m.p. 114°-115° C.

Reference Example 18

To a mixture of 1-benzylspiro[piperidin-4,2'-(4H-1',2'-dihydro-3,1-benzoxadine)] (10.3 g), methanol (80 ml) and sodium cyanoborohydride (2.2 g) is added acetic acid (4.1 ml) in portions and the mixture is stirred at room temperature overnight. The reaction mixture is diluted with water and made alkaline with an aqueous potassium carbonate solution and the formed crystals are separated by filtration to give N-(1-benzyl-4-piperidinyl)-o-hydroxymethylaniline (9.4 g), m.p. 164°-168° C.

Reference Example 19

A mixture of N-(1-benzyl-4-piperidinyl)-o-hydroxymethylaniline (2.9 g), chloroform (100 ml) and manganese dioxide (12 g) is refluxed for 1 hour. After cooling, the mixture is filtered and the filtrate is concentrated. The resulting residue is purified by silica gel column chromatography (eluent; dichloromethane) to give N-(1-benzyl-4-piperidinyl)-o-formylaniline (2.4 g) as yellow powders, m.p. 87°-90° C.

Reference Example 20

A mixture of N-(1-benzyl-4-piperidinyl)-o-formylaniline (32.0 g), diethyl malonate (35.4 g), piperidine (5 ml), acetic acid (2.5 ml), anhydrous toluene (320 ml) and molecular sieves (32 g) is refluxed for 8 hours. After concentrating the reaction mixture, dichloromethane is added to the residue and the mixture is filtered. Water is added to the filtrate and the mixture is extracted with dichloromethane. After concentrating the extract, the resulting residue is purified by silica gel column chromatography (eluent; dichloromethane/methanol=50/1) to give 3-ethoxycarbonyl-1-(1-benzyl-4-piperidinyl)carbostyril (27.2 g).

NMR (CDCl₃) δ: 1.41 (3H, t, J=7.1 Hz), 1.65-1.86 (2H, m), 2.14-2.40 (2H, m), 2.68-3.25 (4H, m), 3.53 (2H, s), 4.41 (2H, q, J=7.1 Hz), 5.28 (1H, brs), 7.16-7.93 (9H, m), 8.30 (1H, s)

Reference Example 21

Using appropriate starting materials, the procedure of Reference Example 1 is repeated to give the following compounds:

N-(1-Benzoyl-4-piperidinyl)-3-fluoroaniline as white powders (recrystallized from ethanol), m.p. 114°-116° C.

N-(1-Benzoyl-4-piperidinyl)-3,5-difluoroaniline as white powders (recrystallized from ethanol), m.p. 175°-176° C.

Reference Example 22

Using appropriate starting materials, the procedure of Reference Examples 17 and 18 is repeated to give the following compound:

N-(1-Benzyl-4-piperidinyl)-2-hydroxymethyl-3-methylaniline as white powders, m.p. 182°-184° C.

Reference Example 23

Using appropriate starting materials, the procedure of Reference Example 19 is repeated to give the following compound:

N-(1-Benzyl-4-piperidinyl)-2-formyl-3-methylaniline as yellow powders, m.p. 114°-116° C.

Reference Example 24

To N-(1-benzyl-4-piperidinyl)-2-formyl-3-methylaniline (7.0 g) are added methanol (100 ml) and methyl (triphenylphosphoranylidene)acetate (15 g) and the mixture is refluxed for 1 hour. After cooling, the formed crystals are separated by filtration to give methyl 2-methyl-5-[(1-benzyl-4-piperidinyl)amino]cinnamate (5.6 g) as pale yellow powders, m.p. 140°-142° C.

Example 1

To N-(1-benzoyl-4-piperidinyl)-2-(2-carbamoylethyl)aniline (85 g) prepared in Reference Example 4 is added 5% hydrochloric acid (500 ml) and the mixture is refluxed for 5 hours. After cooling, the reaction mixture is extracted with diethyl ether and the aqueous layer is made alkaline with a 50% aqueous sodium hydroxide solution and extracted with ethyl acetate. The extract is dried over sodium carbonate and concentrated. The concentrate is purified by silica gel column chromatography (eluent; n-hexane/ethyl acetate=1/0-10/1) and recrystallized from ethanol/n-hexane to give 1-(1-benzoyl-4-piperidinyl)-3,4-dihydrocarbostyril (35 g) as white powders, m.p. 108°-111° C.

Examples 2 to 383C

Using appropriate starting materials, the procedure of Example 1 is repeated to give the following compounds as shown in Table 1. Table 2 shows the NMR analysis of these compounds.

                                      TABLE 1     __________________________________________________________________________      ##STR66##     __________________________________________________________________________     Example 2     Structure      ##STR67##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 82-83° C.     Form: Free     Example 3     Structure      ##STR68##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 142-145° C.     Form: Free     Example 4     Structure      ##STR69##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 108-111° C.     Form: Free     Example 5     Structure      ##STR70##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 113-116° C.     Form: Free     Example 6     Structure      ##STR71##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 105-108° C.     Form: Free     Example 7     Structure      ##STR72##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 129-132° C.     Form: Free     Example 8     Structure      ##STR73##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 161-162° C. (decomposition)     Form: Free     Example 9     Structure      ##STR74##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 194-196° C.     Form: Free     Example 10     Structure      ##STR75##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: double bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 172-174° C.     Form: Free     Example 11     Structure      ##STR76##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 144-147° C.     Form: Free     Example 12     Structure      ##STR77##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 1)     Form: Free     Example 13     Structure      ##STR78##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 143-147° C.     Form: Free     Example 14     Structure      ##STR79##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 143-146° C.     Form: Free     Example 15     Structure      ##STR80##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 138-140° C.     Form: Free     Example 16     Structure      ##STR81##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 143-145° C.     Form: Free     Example 17     Structure      ##STR82##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 2)     Form: Free     Example 18     Structure      ##STR83##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 111-112° C.     Form: Free     Example 19     Structure      ##STR84##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 93-96° C.     Form: Free     Example 20     Structure      ##STR85##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 3)     Form: Free     Example 21     Structure      ##STR86##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 175-178° C.     Form: Free     Example 22     Structure      ##STR87##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 123-126° C.     Form: Free     Example 23     Structure      ##STR88##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 141-143° C.     Form: Free     Example 24     Structure      ##STR89##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether     Melting point: 116-120° C.     Form: Free     Example 25     Structure      ##STR90##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 134-136° C.     Form: Free     Example 26     Structure      ##STR91##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 4)     Form: Free     Example 27     Structure      ##STR92##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 153-155° C.     Form: Free     Example 28     Structure      ##STR93##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 5)     Form: Free     Example 29     Structure      ##STR94##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 6)     Form: Free     Example 30     Structure      ##STR95##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 121-124° C.     Form: Free     Example 31     Structure      ##STR96##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 205-208° C.     Form: Free     Example 32     Structure      ##STR97##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white amorphous     NMR analysis: 7)     Recrystallization solvent: n-hexane     Melting point: 85-90° C.     Form: Free     Example 33     Structure      ##STR98##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 170-171° C.     Form: Free     Example 34     Structure      ##STR99##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 8)     Form: Free     Example 35     Structure      ##STR100##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 124-126° C.     Form: Free     Example 36     Structure      ##STR101##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 105-107° C.     Form: Free     Example 37     Structure      ##STR102##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 169-172° C.     Form: Free     Example 38     Structure      ##STR103##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 85-90° C.     Form: Free     NMR analysis: 9)     Example 39     Structure      ##STR104##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 10)     Form: Free     Example 40     Structure      ##STR105##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 83-86° C.     Form: Free     Example 41     Structure      ##STR106##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 11)     Form: Free     Example 42     Structure      ##STR107##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 161-163° C.     Form: Free     Example 43     Structure      ##STR108##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 108-111° C.     Form: Free     Example 44     Structure      ##STR109##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 202-204° C.     Form: Free     Example 45     Structure      ##STR110##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 194-195° C.     Form: Free     Example 46     Structure      ##STR111##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 110-112° C.     Form: Free     Example 47     Structure      ##STR112##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 123-126° C.     Form: Free     Example 48     Structure      ##STR113##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 198-199° C.     Form: Free     Example 49     Structure      ##STR114##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 160-162° C.     Form: Free     Example 50     Structure      ##STR115##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 12)     Form: Free     Example 51     Structure      ##STR116##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 194-196° C.     Form: Free     Example 52     Structure      ##STR117##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 182-183° C.     Form: Free     Example 53     Structure      ##STR118##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 232-235° C.     Form: Free     Example 54     Structure      ##STR119##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 13)     Form: Free     Example 55     Structure      ##STR120##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 14)     Form: Free     Example 56     Structure      ##STR121##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 15)     Form: Free     Example 57     Structure      ##STR122##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 16)     Form: Free     Example 58     Structure      ##STR123##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 136-138° C.     Form: Free     Example 59     Structure      ##STR124##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 17)     Form: Free     Example 60     Structure      ##STR125##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 18)     Form: Free     Example 61     Structure      ##STR126##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 19)     Form: Free     Example 62     Structure      ##STR127##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 184-186° C.     Form: Free     Example 63     Structure      ##STR128##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 139-140° C.     Form: Free     Example 64     Structure      ##STR129##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 238-240° C.     Form: Free     Example 65     Structure      ##STR130##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 224-226° C.     Form: Free     Example 66     Structure      ##STR131##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 110-111° C.     Form: Free     Example 67     Structure      ##STR132##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 220-222° C. (decomposition)     Form: Free     Example 68     Structure      ##STR133##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 20)     Form: Free     Example 69     Structure      ##STR134##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 21)     Form: Free     Example 70     Structure      ##STR135##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 22)     Form: Free     Example 71     Structure      ##STR136##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 98-99° C.     Form: Free     Example 72     Structure      ##STR137##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 84-87° C.     Form: Free     Example 73     Structure      ##STR138##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 138-139° C.     Form: Free     Example 74     Structure      ##STR139##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 95-98° C.     Form: Free     Example 75     Structure      ##STR140##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 240-243° C. (decomposition)     Form: Free     Example 76     Structure      ##STR141##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 93-96° C. (decomposition)     Form: Free     Example 77     Structure      ##STR142##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 23)     Form: Free     Example 78     Structure      ##STR143##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale red powders     Recrystallization solvent: n-hexane     Melting point: 104-107° C.     Form: Free     Example 79     Structure      ##STR144##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 24)     Form: Free     Example 80     Structure      ##STR145##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 113-116° C.     Form: Free     Example 81     Structure      ##STR146##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale grey powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 162-164° C.     Form: Free     Example 82     Structure      ##STR147##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 25)     Form: Free     Example 83     Structure      ##STR148##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 93-96° C.     Form: Free     Example 84     Structure      ##STR149##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 26)     Form: Free     Example 85     Structure      ##STR150##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 144-146° C.     Form: Free     Example 86     Structure      ##STR151##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 197-199° C.     Form: Free     Example 87     Structure      ##STR152##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 27)     Form: Free     Example 88     Structure      ##STR153##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 28)     Form: Free     Example 89     Structure      ##STR154##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 29)     Form: Free     Example 90     Structure      ##STR155##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 30)     Form: Free     Example 91     Structure      ##STR156##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 193-196° C.     Form: Free     Example 92     Structure      ##STR157##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 82-85° C.     Form: Free     Example 93     Structure      ##STR158##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 31)     Form: Free     Example 94     Structure      ##STR159##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 32)     Form: Free     Example 95     Structure      ##STR160##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 122-125° C.     Form: Free     Example 96     Structure      ##STR161##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 168-171° C.     Form: Free     Example 97     Structure      ##STR162##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 213-215° C.     Form: Free     Example 98     Structure      ##STR163##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 111-114° C.     Form: Free     Example 99     Structure      ##STR164##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 33)     Form: Free     Example 100     Structure      ##STR165##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 222-224° C.     Form: Free     Example 101     Structure      ##STR166##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 149-151° C.     Form: Free     Example 102     Structure      ##STR167##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: n-hexane/ethanol     Melting point: 174-175° C.     Form: Free     Example 103     Structure      ##STR168##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 130-132° C.     Form: Free     Example 104     Structure      ##STR169##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale grey powders     Recrystallization solvent: n-hexane     Melting point: 153-156° C.     Form: Free     Example 105     Structure      ##STR170##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 134-136° C.     Form: Free     Example 106     Structure      ##STR171##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     MR analysis: 34)     Form: Free     Example 107     Structure      ##STR172##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: water     Melting point: 92-97° C.     Form: Free     NMR analysis: 35)     Example 108     Structure      ##STR173##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 36)     Form: Free     Example 109     Structure      ##STR174##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 37)     Form: Free     Example 110     Structure      ##STR175##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 38)     Form: Free     Example 111     Structure      ##STR176##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 40)     Form: Free     Example 112     Structure      ##STR177##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 41)     Form: Free     Example 113     Structure      ##STR178##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 42)     Form: Free     Example 114     Structure      ##STR179##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 43)     Form: Free     Example 115     Structure      ##STR180##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 44)     Form: Free     Example 116     Structure      ##STR181##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 45)     Form: Free     Example 117     Structure      ##STR182##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 46)     Form: Free     Example 118     Structure      ##STR183##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 47)     Form: Free     Example 119     Structure      ##STR184##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 48)     Form: Free     Example 120     Structure      ##STR185##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 49)     Form: Free     Example 121     Structure      ##STR186##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 50)     Form: Free     Example 122     Structure      ##STR187##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 51)     Form: Free     Example 123     Structure      ##STR188##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 52)     Form: Free     Example 124     Structure      ##STR189##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 53)     Form: Free     Example 125     Structure      ##STR190##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 54)     Form: Free     Example 126     Structure      ##STR191##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 55)     Form: Free     Example 127     Structure      ##STR192##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 56)     Form: Free     Example 128     Structure      ##STR193##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 57)     Form: Free     Example 129     Structure      ##STR194##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 58)     Form: Free     Example 130     Structure      ##STR195##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 59)     Form: Free     Example 131     Structure      ##STR196##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 60)     Form: Free     Example 132     Structure      ##STR197##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 67-69° C.     Form: Free     Example 133     Structure      ##STR198##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 61)     Form: Free     Example 134     Structure      ##STR199##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 136-138° C.     Form: Free     Example 135     Structure      ##STR200##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether     Melting point: 171-173° C.     Form: Free     Example 136     Structure      ##STR201##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 62)     Form: Free     Example 137     Structure      ##STR202##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 63)     Form: Free     Example 138     Structure      ##STR203##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 64)     Form: Free     Example 139     Structure      ##STR204##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 65)     Form: Free     Example 140     Structure      ##STR205##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 66)     Form: Free     Example 141     Structure      ##STR206##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether     Melting point: 147.5-149° C.     Form: Free     NMR analysis: 67)     Example 142     Structure      ##STR207##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol     Melting point: 136-138° C.     Form: Free     NMR analysis: 68)     Example 143     Structure      ##STR208##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 69)     Form: Free     Example 144     Structure      ##STR209##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 70)     Form: Free     Example 145     Structure      ##STR210##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 71)     Form: Free     Example 146     Structure      ##STR211##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 72)     Form: Free     Example 147     Structure      ##STR212##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 73)     Form: Free     Example 148     Structure      ##STR213##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 74)     Form: Free     Example 149     Structure      ##STR214##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 75)     Form: Free     Example 150     Structure      ##STR215##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 76)     Form: Free     Example 151     Structure      ##STR216##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 77)     Form: Free     Example 152     Structure      ##STR217##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 78)     Form: Free     Example 153     Structure      ##STR218##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 79)     Form: Free     Example 154     Structure      ##STR219##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 80)     Form: Free     Example 155     Structure      ##STR220##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 81)     Form: Free     Example 156     Structure      ##STR221##     R.sup.1 : 7-C.sub.2 H.sub.5     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 82)     Form: Free     Example 157     Structure      ##STR222##     R.sup.1 : 7-C.sub.2 H.sub.5     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 83)     Form: Free     Example 158     Structure      ##STR223##     R.sup.1 : 7-OCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 84)     Form: Free     Example 159     Structure      ##STR224##     R.sup.1 : 7-OCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 85)     Form: Free     Example 160     Structure      ##STR225##     R.sup.1 :      ##STR226##     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 86)     Form: Free     Example 161     Structure      ##STR227##     R.sup.1 : 6-NHCOCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol     Melting point: 271-272° C.     Form: Free     Example 162     Structure      ##STR228##     R.sup.1 : 6-NH.sub.2     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 87)     Form: Free     Example 163     Structure      ##STR229##     R.sup.1 : 6-NO.sub.2     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: ethanol     Melting point: 197-199° C.     Form: Free     Example 164     Structure      ##STR230##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 151.5-152.5° C.     Form: Free     Example 165     Structure      ##STR231##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: double bond     NMR analysis: 88)     Form: Free     Example 166     Structure      ##STR232##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 89)     Form: Free     Example 167     Structure      ##STR233##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: double bond     NMR analysis: 90)     Form: Free     Example 168     Structure      ##STR234##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: double bond     NMR analysis: 91)     Form: Free     Example 169     Structure      ##STR235##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 181-183° C.     Form: Free     Example 170     Structure      ##STR236##     R.sup.1 : 6-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 92)     Form: Free     Example 171     Structure      ##STR237##     R.sup.1 : 6-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 93)     Form: Free     Example 172     Structure      ##STR238##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 94)     Form: Free     Example 173     Structure      ##STR239##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 95)     Form: Free     Example 174     Structure      ##STR240##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 96)     Form: Free     Example 175     Structure      ##STR241##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether     Melting point: 151-154° C.     Form: Free     Example 176     Structure      ##STR242##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol     Melting point: 169-171° C.     Form: Free     Example 177     Structure      ##STR243##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 97)     Form: Free     Example 178     Structure      ##STR244##     R.sup.1 : 6-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 98)     Form: Free     Example 179     Structure      ##STR245##     R.sup.1 : 8-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 99)     Form: Free     Example 180     Structure      ##STR246##     R.sup.1 : 7-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 100)     Form: Free     Example 181     Structure      ##STR247##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 101)     Form: Free     Example 182     Structure      ##STR248##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 183-183.5° C.     Form: Free     Example 183     Structure      ##STR249##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 175-176° C.     Form: Free     Example 184     Structure      ##STR250##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 102)     Form: Free     Example 185     Structure      ##STR251##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 291-292° C.     Form: Free     Example 186     Structure      ##STR252##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 215-216° C.     Form: Free     Example 187     Structure      ##STR253##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 103)     Form: Free     Example 188     Structure      ##STR254##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 104)     Form: Free     Example 189     Structure      ##STR255##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 140.5-142° C.     Form: Free     Example 190     Structure      ##STR256##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 164-164.5° C.     Form: Free     Example 191     Structure      ##STR257##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/methanol/diethyl ether     Melting point: 156-158° C.     Form: Free     Example 192     Structure      ##STR258##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether     Melting point: 158-166° C.     Form: Hydrochloride     Example 193     Structure      ##STR259##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/methanol     Melting point: 245-249° C.     Form: Free     Example 194     Structure      ##STR260##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/diethyl ether     Melting point: 159-161° C.     Form: Free     Example 195     Structure      ##STR261##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow needles     Recrystallization solvent: methanol/chloroform/diethyl ether     Melting point: 207-209° C.     Form: Free     Example 196     Structure      ##STR262##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 177-180° C.     Form: Free     Example 197     Structure      ##STR263##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether/n-hexane     Melting point: 145-150° C.     Form: Free     Example 198     Structure      ##STR264##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless flakes     Recrystallization solvent: ethyl acetate/ethanol     Melting point: 209-211° C.     Form: Free     Example 199     Structure      ##STR265##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 105)     Form: Free     Example 200     Structure      ##STR266##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether     Melting point: 141-143° C.     Form: Free     Example 201     Structure      ##STR267##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 106:     Form: Free     Example 202     Structure      ##STR268##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethyl acetate/diethyl ether/n-hexane     Melting point: 148-150° C.     Form: Free     Example 203     Structure      ##STR269##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 169-172° C.     Form: Free     Example 204     Structure      ##STR270##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethyl acetate/diethyl ether/n-hexane     Melting point: 144-146° C.     Form: Free     Example 205     Structure      ##STR271##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 107)     Form: Free     Example 206     Structure      ##STR272##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless flakes     Recrystallization solvent: ethyl acetate/diethyl ether/n-hexane     Melting point: 181-183° C.     Form: Free     Example 207     Structure      ##STR273##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether/n-hexane     Melting point: 141-144° C.     Form: Free     Example 208     Structure      ##STR274##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/diethyl ether     Melting point: 234-236° C.     Form: Free     Example 209     Structure      ##STR275##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether     Melting point: 117-119° C.     Form: Free     Example 210     Structure      ##STR276##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 116-120° C.     Form: Free     Example 211     Structure      ##STR277##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 87-90° C.     Form: Free     Example 212     Structure      ##STR278##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 171.5-172.5° C.     Form: Free     Example 213     Structure      ##STR279##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 159.5-160° C.     Form: Free     Example 214     Structure      ##STR280##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 168-169° C.     Form: Free     Example 215     Structure      ##STR281##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 188-189° C.     Form: Free     Example 216     Structure      ##STR282##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 295° C. (decomposition)     Form: Free     Example 217     Structure      ##STR283##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 131.5-132.5° C.     Form: Free     Example 218     Structure      ##STR284##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 159-160° C.     Form: Free     Example 219     Structure      ##STR285##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 172-172.5° C.     Form: Free     Example 220     Structure      ##STR286##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 108)     Form: Free     Example 221     Structure      ##STR287##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 109)     Form: Free     Example 222     Structure      ##STR288##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 154-154.5° C.     Form: Free     Example 223     Structure      ##STR289##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 97-99° C.     Form: Free     Example 224     Structure      ##STR290##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 110)     Form: Free     Example 225     Structure      ##STR291##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 111)     Form: Free     Example 226     Structure      ##STR292##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 112-113.5° C.     Form: Free     Example 227     Structure      ##STR293##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 112)     Form: Free     Example 228     Structure      ##STR294##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether     Melting point: 134-137° C.     Form: Free     Example 229     Structure      ##STR295##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 113)     Form: Free     Example 230     Structure      ##STR296##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 114)     Form: Free     Example 231     Structure      ##STR297##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 115)     Form: Free     Example 232     Structure      ##STR298##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 116)     Form: Free     Example 233     Structure      ##STR299##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization ethanol/diethyl ether/n-hexane     Melting point: 162-163° C.     Form: Free     Example 234     Structure      ##STR300##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 117)     Form: Free     Example 235     Structure      ##STR301##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 118)     Form: Free     Example 236     Structure      ##STR302##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 119)     Form: Free     Example 237     Structure      ##STR303##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 120)     Form: Free     Example 238     Structure      ##STR304##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 179-180° C.     Form: Free     Example 239     Structure      ##STR305##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 188-189° C.     Form: Free     Example 240     Structure      ##STR306##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 217-218° C.     Form: Free     Example 241     Structure      ##STR307##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 121)     Form: Free     Example 242     Structure      ##STR308##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 122)     Form: Hydrochloride     Example 243     Structure      ##STR309##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 123)     Form: Free     Example 244     Structure      ##STR310##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 279-280° C.     Form: Free     Example 245     Structure      ##STR311##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 155-156° C.     Form: Free     Example 246     Structure      ##STR312##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 124)     Form: Free     Example 247     Structure      ##STR313##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 125)     Form: Free     Example 248     Structure      ##STR314##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 126)     Form: Free     Example 249     Structure      ##STR315##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 127)     Form: Free     Example 250     Structure      ##STR316##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 128)     Form: Free     Example 251     Structure      ##STR317##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 129)     Form: Free     Example 252     Structure      ##STR318##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 130)     Form: Free     Example 253     Structure      ##STR319##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 131)     Form: Free     Example 254     Structure      ##STR320##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 146-148° C.     Form: Free     Example 255     Structure      ##STR321##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 132)     Form: Free     Example 256     Structure      ##STR322##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 133)     Form: Free     Example 257     Structure      ##STR323##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 134)     Form: Free     Example 258     Structure      ##STR324##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 135)     Form: Free     Example 259     Structure      ##STR325##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 136)     Form: Free     Example 260     Structure      ##STR326##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/water     Melting point: 90-91° C.     Form: Free     Example 261     Structure      ##STR327##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 137)     Form: Free     Example 262     Structure      ##STR328##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 138)     Form: Free     Example 263     Structure      ##STR329##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 139)     Form: Free     Example 264     Structure      ##STR330##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 140)     Form: Free     Example 265     Structure      ##STR331##     R.sup.1 : 7-N(CH.sub.3).sub.2     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 141)     Form: Free     Example 266     Structure      ##STR332##     R.sup.1 : 4-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 142)     Form: Free     Example 267     Structure      ##STR333##     R.sup.1 : 7-NHCOCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol     Melting point: 176-178° C.     Form: Free     Example 268     Structure      ##STR334##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/acetone/diethyl ether     Melting point: 222-226° C.     Form: Hydrochloride     Example 269     Structure      ##STR335##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 143)     Form: Free     Example 270     Structure      ##STR336##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/acetone/diethyl ether     Melting point: 89-93° C.     Form: Hydrochloride     Example 271     Structure      ##STR337##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 144)     Form: Free     Example 272     Structure      ##STR338##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 90-92° C.     Form: Free     Example 273     Structure      ##STR339##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 139-139.5° C.     Form: Free     Example 274     Structure      ##STR340##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 145)     Form: Free     Example 275     Structure      ##STR341##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol     Melting point: 101.5-103.5° C.     Form: Free     Example 276     Structure      ##STR342##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol     Melting point: 115-117° C.     Form: Free     Example 277     Structure      ##STR343##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 146)     Form: Free     Example 278     Structure      ##STR344##     R.sup.1 : 6-OCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 147)     Form: Free     Example 279     Structure      ##STR345##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 148)     Form: Free     Example 280     Structure      ##STR346##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 149)     Form: Free     Example 281     Structure      ##STR347##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 150)     Form: Free     Example 282     Structure      ##STR348##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: dichloromethane/n-hexane     Melting point: 158-160° C.     Form: Free     Example 283     Structure      ##STR349##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethyl acetate/diethyl ether     Melting point: 171-174° C.     Form: Free     Example 284     Structure      ##STR350##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 151)     Form: Free     Example 285     Structure      ##STR351##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless flakes     Recrystallization solvent: ethanol     Melting point: 138-140° C.     Form: Free     Example 286     Structure      ##STR352##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: dichloromethane/ethanol     Melting point: 237-240° C.     Form: Free     Example 287     Structure      ##STR353##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 152)     Form: Free     Example 288     Structure      ##STR354##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless flakes     Recrystallization solvent: methanol/water     Melting point: 169-171° C.     Form: Free     Example 289     Structure      ##STR355##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 153)     Form: Free     Example 290     Structure      ##STR356##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 154)     Form: Free     Example 291     Structure      ##STR357##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 226-227° C.     Form: Free     Example 292     Structure      ##STR358##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 155)     Form: Free     Example 293     Structure      ##STR359##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 254-255° C.     Form: Free     Example 294     Structure      ##STR360##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 156)     Form: Free     Example 295     Structure      ##STR361##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 157)     Form: Free     Example 296     Structure      ##STR362##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 158)     Form: Free     Example 297     Structure      ##STR363##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 159)     Form: Free     Example 298     Structure      ##STR364##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 160)     Form: Free     Example 299     Structure      ##STR365##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 161)     Form: Free     Example 300     Structure      ##STR366##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/n-hexane     Melting point: 156-157° C.     Form: Free     Example 301     Structure      ##STR367##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/water     Melting point: 175-176° C.     Form: Free     Example 302     Structure      ##STR368##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 162)     Form: Free     Example 303     Structure      ##STR369##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/water     Melting point: 229.5-231° C.     Form: Free     Example 304     Structure      ##STR370##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/water     Melting point: 132-133° C.     Form: Free     Example 305     Structure      ##STR371##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 163)     Form: Free     Example 306     Structure      ##STR372##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 164)     Form: Free     Example 307     Structure      ##STR373##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 165)     Form: Free     Example 308     Structure      ##STR374##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/water     Melting point: 146-148° C.     Form: Free     Example 309     Structure      ##STR375##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 166)     Form: Free     Example 310     Structure      ##STR376##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/water     Melting point: 179.5-181.5° C.     Form: Free     Example 311     Structure      ##STR377##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 166A)     Form: Free     Example 312     Structure      ##STR378##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 167)     Form: Free     Example 313     Structure      ##STR379##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 168)     Form: Free     Example 314     Structure      ##STR380##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 169)     Form: Free     Example 315     Structure      ##STR381##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 170)     Form: Free     Example 316     Structure      ##STR382##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/water     Melting point: 110-112° C.     Form: Free     Example 317     Structure      ##STR383##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 175.5-176.5° C.     Form: Free     Example 318     Structure      ##STR384##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 171)     Form: Free     Example 319     Structure      ##STR385##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 172)     Form: Free     Example 320     Structure      ##STR386##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 173)     Form: Free     Example 321     Structure      ##STR387##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 174)     Form: Free     Example 322     Structure      ##STR388##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 175)     Form: Free     Example 323     Structure      ##STR389##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 176)     Form: Free     Example 324     Structure      ##STR390##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 177)     Form: Free     Example 325     Structure      ##STR391##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 178)     Form: Free     Example 326     Structure      ##STR392##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 179)     Form: Free     Example 327     Structure      ##STR393##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 180)     Form: Free     Example 328     Structure      ##STR394##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 181)     Form: Free     Example 329     Structure      ##STR395##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 101-104° C.     Form: Free     Example 330     Structure      ##STR396##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 146-147° C.     Form: Free     Example 331     Structure      ##STR397##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: pale yellow powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 95-98° C.     Form: Free     Example 332     Structure      ##STR398##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 94-97° C.     Form: (COOH).sub.2     Example 333     Structure      ##STR399##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 101-102° C.     Form: Free     Example 334     Structure      ##STR400##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether     Melting point: 72-76° C.      ##STR401##     Example 335     Structure      ##STR402##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 87-89° C.     Form: Free     Example 336     Structure      ##STR403##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 70-72° C.     Form: Free     Example 337     Structure      ##STR404##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 94-96° C.     Form: Free     Example 338     Structure      ##STR405##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 108-109° C.     Form: Free     Example 339     Structure      ##STR406##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane/ethanol     Melting point: 103-104° C.     Form: Free     Example 340     Structure      ##STR407##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 114-116° C.     Form: Free     Example 341     Structure      ##STR408##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 133-134° C.     Form: Free     Example 342     Structure      ##STR409##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 85-86° C.     Form: Free     Example 343     Structure      ##STR410##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: n-hexane     Melting point: 121-122° C.     Form: Free     Example 344     Structure      ##STR411##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 71-73° C.     Form: Free     Example 345     Structure      ##STR412##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 182)     Form: Free     Example 346     Structure      ##STR413##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 183)     Form: Free     Example 347     Structure      ##STR414##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 184)     Form: Free     Example 348     Structure      ##STR415##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 185)     Form: Free     Example 349     Structure      ##STR416##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 186)     Form: Free     Example 350     Structure      ##STR417##     R.sup.1 : 6-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 187)     Form: Free     Example 351     Structure      ##STR418##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 188)     Form: Free     Example 352     Structure      ##STR419##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 189)     Form: Free     Example 353     Structure      ##STR420##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 190)     Form: Free     Example 354     Structure      ##STR421##     R.sup.1 : 6-OCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 191)     Form: Free     Example 355     Structure      ##STR422##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 192)     Form: Free     Example 356     Structure      ##STR423##     R.sup.1 : 7-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 193)     Form: Free     Example 357     Structure      ##STR424##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR Analysis: 194)     Form: Free     Example 358     Structure      ##STR425##     R.sup.1 : 8-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 195)     Form: Free     Example 359     Structure      ##STR426##     R.sup.1 : 7-NHCOCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 196)     Form: Free     Example 360     Structure      ##STR427##     R.sup.1 : 4-CH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 197)     Form: Free     Example 361     Structure      ##STR428##     R.sup.1 : 7-N(CH.sub.3).sub.2     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 198)     Form: Free     Example 362     Structure      ##STR429##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 199)     Form: Free     Example 363     Structure      ##STR430##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 200)     Form: Free     Example 364     Structure      ##STR431##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 201)     Form: Free     Example 365     Structure      ##STR432##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless needles     Recrystallization solvent: ethanol/water     Melting point: 146-148° C.     Form: Free     Example 366     Structure      ##STR433##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/diethyl ether/n-hexane     Melting point: 181-183° C.     Form: Free     Example 367     Structure      ##STR434##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol     Melting point: 99-101° C.     Form: Free     Example 368     Structure      ##STR435##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/n-hexane     Melting point: 83-86° C.     Form: Free     Example 369     Structure      ##STR436##     R.sup.1 : 7-C.sub.2 H.sub.5     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 202)     Form: Free     Example 370     Structure      ##STR437##     R.sup.1 : 7-OCH.sub.3     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 203)     Form: Free     Example 371     Structure      ##STR438##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 204)     Form: Free     Example 372     Structure      ##STR439##     R.sup.1 : 7-F     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: ethanol/water     Melting point: 159-161° C.     Form: Free     Example 373     Structure      ##STR440##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 205)     Form: Free     Example 374     Structure      ##STR441##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 206)     Form: Free     Example 375     Structure      ##STR442##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless flakes     Recrystallization solvent: diethyl ether     Melting point: 175-176° C.     Form: Free     Example 376     Structure      ##STR443##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether     Melting point: 199-200° C.     Form: Free     Example 377     Structure      ##STR444##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether     Melting point: 167-168° C.     Form: Free     Example 378     Structure      ##STR445##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 136-137° C.     Form: Free     Example 379     Structure      ##STR446##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 154-155° C.     Form: Free     Example 380     Structure      ##STR447##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 167-168° C.     Form: Free     Example 381     Structure      ##STR448##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 189-191° C.     Form: Free     Example 382     Structure      ##STR449##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 215-216° C.     Form: Free     Example 383     Structure      ##STR450##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: white powders     Recrystallization solvent: diethyl ether/n-hexane     Melting point: 199-200° C.     Form: Free     Example 383A     Structure      ##STR451##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 207)     Form: Free     Example 383B     Structure      ##STR452##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     Crystalline form: colorless prisms     Recrystallization solvent: ethanol/ethyl acetate     Melting point: 141-142° C.     NMR analysis: 208)     Form: Free     Example 383C     Structure      ##STR453##     R.sup.1 : H     Bond between 3- and 4-positions in the     carbostyril ring: single bond     NMR analysis: 209)     Form: Free     __________________________________________________________________________

                  TABLE 2     ______________________________________     No.      NMR (CDCl.sub.3) δ value     ______________________________________      1       1.55-1.82(2H, m), 2.08-2.87(7H, m),              2.95-3.17(1H, m), 3.79(2H, s),              3.90-4.08(1H, m), 4.35-4.58(1H, m),              4.73-4.92(1H, m), 6.86-7.48(9H, m)      2       1.65-1.84(2H, m), 2.25-2.88(7H, m),              3.05-3.24(1H, m), 3.97(2H, s),              4.00-4.13(1H, m), 4.38-4.58(1H, m),              4.73-4.92(1H, m), 6.92-7.28(7H, m)      3       1.72-2.01(2H, m), 2.53-3.01(7H, m),              3.13-3.33(1H, m), 4.09-4.23(1H, m),              4.43-4.62(1H, m), 4.87-5.04(1H, m),              6.97-7.33(4H, m), 8.55(1H, dd, J=2.5, 1.4Hz),              8.64(1H, d, J=2.5Hz), 8.99(1H, d, J=1.4Hz)      4       0.98(3H, t, J=7.3Hz), 1.40-1.93(6H, m),              2.50-3.15(8H, m), 3.99(2H, t, J=6.4Hz),              3.13-5.10(3H, m), 6.83-7.48(4H, m)      5       1.46-1.86(8H, m), 2.33-3.04(8H, m),              3.95-5.10(8H, m), 6.02-6.20(1H, m),              6.96-7.40(9H, m)      6       1.65-1.93(2H, m), 2.50(3H, s),              2.52-3.24(8H, m), 3.56-5.25(3H, m),              6.95-7.46(8H, m)      7       1.65-1.96(2H, m), 2.18(3H, s),              2.46-3.18(8H, m), 3.72-5.13(3H, m),              6.95-7.32(4H, m), 7.32-7.56(4H, m),              7.95(1H, brs)      8       1.20-3.33(20H, m), 3.85-5.85(8H, m),              6.96-7.29(4H, m)      9       1.12-1.93(2H, m), 2.52-3.30(8H, m),              4.00(3H, s), 3.73-5.15(3H, m)              7.00-7.34(5H, m), 7.72(1H, dd, J=8.6, 2.1Hz),              7.99(1H, d, J=2.1Hz)      10      1.63-2.04(2H, m), 2.52-3.24(8H, m),              2.63(3H, s), 3.71-3.89(1H, m),              4.26-4.44(1H, m), 4.80-5.04(1H, m),              7.00-7.33(4H, m), 7.56(2H, d, J=8.0Hz),              8.01(2H, d, J=8.0Hz)      11      1.33(3H, t, J=7.3Hz), 1.68-2.06(2H, m),              2.50-3.30(8H, m), 3.13(2H, q, J=7.3Hz),              3.72-5.13(3H, m), 6.97-7.34(6H, m),              7.44(2H, d, J=8.5Hz), 7.58(2H, d, J=8.5Hz)      12      1.72-1.98(2H, m), 2.54-3.20(8H, m),              3.84-5.08(3H, m), 5.13(2H, s),              6.98-7.52(13H, m)      13      1.58-1.73(1H, m), 1.78-1.96(1H, m),              2.50(3H, s), 2.42-3.26(8H, m),              3.56-3.73(1H, m), 3.28-3.97(3H, m),              4.20-4.73(1H, m), 4.88-5.05(1H, m)              6.78-6.92(2H, m), 6.98-7.36(4H, m)      14      1.72-1.94(2H, m), 2.48-3.26(10H, m),              2.66(6H, s), 3.77-5.28(5H, m),              6.94-7.45(6H, m)      15      1.03(6H, d, J=6.7Hz), 1.70-1.90(2H, m),              1.95-2.22(1H, m), 2.47-3.18(8H, m),              3.74(2H, d, J=6.5Hz), 3.66-5.10(3H, m),              6.84-7.49(8H, m)      16      1.47(9H, s), 1.68-1.97(2H, m),              2.50-3.22(8H, m), 3.28(3H, s),              3.66-5.10(3H, m), 6.96-7.52(8H, m)      17      1.45(9H, s), 1.55(3H, s), 1.69(3H, s),              1.60-1.94(2H, m), 2.50-3.23(8H, m),              3.72-5.14(3H, m), 4.22(2H, d, J=6.4Hz),              5.20-5.33(1H, m), 6.98-7.44(8H, m)      18      1.68-1.93(2H, m), 2.50-3.34(16H, m),              3.90-4.97(3H, m), 6.89(2H, d, J=8.8Hz),              6.98-7.31(4H, m), 7.41(2H, d, J=8.8Hz)      19      1.56-1.79(2H, m), 1.75(3H, s),              1.80(3H, s), 2.47-3.14(8H, m),              3.93-5.05(3H, m), 4.53(2H, d, J=6.8Hz),              5.40-5.57(1H, m), 6.83-7.53(8H, m)      20      1.70-1.90(2H, m), 2.36(3H, s),              2.43-3.12(12H, m), 3.22-3.35(4H, m),              3.92-4.86(3H, m), 6.89(2H, d, J=8.8Hz),              6.96-7.32(4H, m), 7.41(2H, d, J=8.8Hz)      21      1.25(6H, d, J=6.9Hz), 1.63-2.00(2H, m),              2.49-3.27(9H, m), 3.70-5.20(3H, m),              6.97-7.47(8H, m)      22      1.68-2.07(2H, m), 2.50-3.30(8H, m),              3.70-3.93(1H, m), 4.28-4.45(1H, m),              4.83-4.58(1H, m), 7.02-7.33(4H, m),              7.62-7.69(2H, m), 7.93-8.01(2H, m),              10.08(1H, s)      23      1.72-2.29(6H, m), 2.39-2.92(7H, m),              3.10-3.32(1H, m), 3.35-3.65(2H, m),              3.82-4.25(2H, m), 4.52-4.90(2H, m),              6.30-7.35(5H, m)      24      1.72-1.92(2H, m), 2.52-3.12(8H, m),              3.72-3.88(2H, m), 4.07(1H, brs),              4.15-4.76(3H, m), 5.14-5.35(2H, m),              5.83-6.04(1H, m), 6.56-6.62(2H, m),              6.98-7.37(6H, m)      25      1.72-1.90(2H, m), 2.52-3.10(8H, m),              2.99(3H, s), 3.93-4.02(2H, m),              4.23-4.68(3H, m), 5.08-5.21(2H, m),              5.72-5.94(1H, m), 6.61-6.75(2H, m),              6.96-7.32(4H, m), 7.35-7.46(2H, m)      26      1.63-2.05(2H, m), 2.52-3.23(8H, m),              3.18(3H, s), 3.59-5.18(3H, m),              6.98-7.42(6H, m), 7.52-7.62(2H, m)      27      1.65-1.97(2H, m), 2.48-3.22(8H, m),              3.73-5.15(3H, m), 5.20(2H, s),              6.98-7.45(13H, m)      28      1.61-1.95(2H, m), 2.44-3.22(8H, m),              3.33(3H, s), 3.59-3.74(1H, m),              3.75-3.92(3H, m), 4.29-4.72(1H, m),              4.89-5.08(1H, m), 5.18(2H, s),              6.80-7.42(12H, m)      29      1.56-1.95(2H, m), 2.45-3.28(8H, m),              2.85(3H, s), 3.62-4.03(5H, m),              4.32-5.12(2H, m), 6.10(1H, d, J=2.0Hz),              6.20(1H, dd, J=8.2, 2.0Hz), 6.95-7.31(4H, m)      30      0.77-1.98(23H, m), 2.28-3.22(10H, m),              3.90-4.08(1H, m), 4.32-4.53(1H, m),              4.73-4.94(1H, m), 6.93-7.33(4H, m)      31      1.33(9H, s), 1.58-2.01(2H, m),              2.48-3.21(8H, m), 3.77-5.11(3H, m),              6.99-7.31(4H, m), 7.41(4H, s)      32      1.68-1.96(2H, m), 2.48-3.22(8H, m),              2.54(1H, s), 3.82-5.32(3H, m),              4.72(2H, d, J=2.4Hz), 6.92-7.33(6H, m),              7.38-7.52(2H, m)      33      1.60-1.92(2H, m), 1.61(3H, s), 1.68(3H, s),              1.75(3H, s), 1.95-2.22(4H, m),              2.51-3.15(8H, m), 3.88-4.93(3H, m),              4.56(2H, d, J=6.6Hz), 5.04-5.18(1H, m),              5.42-5.56(1H, m), 6.88-7.32(6H, m),              7.38-7.48(2H, m)      34      1.20-2.10(12H, m), 2.44-3.13(8H, m),              3.78-5.08(4H, m), 6.90(2H, d, J=8.7Hz),              6.97-7.32(4H, m), 7.40(2H, d, J=8.7Hz)              DMSO-d.sub.6      35      1.55-1.92(2H, m), 2.32-3.05(7H, m),              3.12-3.62(2H, m), 4.22-4.72(2H, m),              6.92-7.38(4H, m), 7.63(2H, d, J=8.2Hz),              7.92(2H, d, J=8.2Hz), 9.48(3H, brs)              MS(m/e) = 377(m.sup.+)              CDCl.sub.3      36      0.85-1.02(3H, m), 1.25-1.60(6H, m),              1.70-1.92(4H, m), 2.52-3.16(8H, m),              3.98(2H, t, J=6.5Hz), 3.86-5.06(3H, m),              6.84-6.96(2H, m), 6.98-7.33(4H, m),              7.38-7.50(2H, m)      37      0.80-0.96(3H, m), 1.18-1.55(18H, m),              1.68-1.92(4H, m), 2.51-3.11(8H, m),              3.78-5.05(3H, m), 3.97(2H, t, J=6.5Hz),              6.84-6.98(2H, m), 7.00-7.32(4H, m),              7.38-7.50(2H, m)      38      1.68-1.94(2H, m), 2.08-2.26(2H, m),              2.48-3.21(10H, m), 3.81-5.10(3H, m),              4.11(2H, t, J=5.7Hz), 6.91(2H, d, J=8.8Hz),              6.98-8.30(4H, m), 7.44(2H, d, J=8.8Hz)      40      1.26(3H, t, J=7.1Hz), 1.70-2.10(4H, m),              2.42(2H, t, J=7.0Hz), 2.49-3.31(10H, m),              4.14(2H, q, J=7.1Hz), 3.93-4.28(4H, m),              6.57(2H, d, J=8.6Hz), 6.95-7.33(4H, m),              7.34(2H, d, J=8.6Hz)      41      1.21(3H, t, J=7.1Hz), 1.55-1.95(2H, m),              2.42-3.05(10H, m), 2.94(2H, t, J=7.3Hz),              3.70-5.02(5H, m), 4.14(2H, q, J=7.1Hz),              5.28-5.95(1H, m), 6.90-7.25(6H, m),              7.32(2H, d, J=8.1Hz)      42      1.43-1.70(2H, m), 1.71-1.96(2H, m),              2.09-2.35(2H, m), 2.45-3.18(8H, m),              3.76-5.04(5H, m), 6.84-7.43(8H, m),              8.42-9.13(3H, m)      43      1.56-1.83(2H, m), 2.01-2.21(2H, m),              2.43-3.11(12H, m), 3.49-3.61(4H, m),              3.70(3H, s), 3.62-4.95(7H, m),              6.71-6.90(6H, m), 6.92-7.25(4H, m),              7.30-7.45(2H, m)      44      1.63-1.86(2H, m), 2.02-2.22(2H, m),              2.44-3.21(12H, m), 3.42-3.70(4H, m),              3.68-4.97(7H, m), 6.72-7.43(12H, m)      45      1.65-1.98(2H, m), 2.49-3.22(8H, m),              3.78(3H, s), 3.75-5.07(3H, m),              6.96-7.32(5H, m), 7.43(4H, s)      46      1.05-1.33(3H, m), 1.66-2.02(2H, m),              2.30-3.26(10H, m), 3.83-5.13(3H, m),              5.69-5.83, 6.35-6.75(2H, m), 7.02-7.54(8H, m)      47      1.42-2.16(6H, m), 2.18-2.45(8H, m),              2.52-3.18(8H, m), 3.28-5.12(7H, m),              6.90(2H, d, J=8.6Hz), 6.97-7.30(4H, m),              7.42(2H, d, J=8.6Hz)      48      1.48-2.14(6H, m), 2.35-3.18(13H, m),              3.53-5.02(8H, m), 6.90(2H, d, J=8.7Hz),              6.98-7.29.(4H, m), 7.41(2H, d, J=8.7Hz)      49      1.58-1.88(2H, m), 2.03-2.25(2H, m),              2.45-3.13(10H, m), 3.67-5.03(5H, m),              6.86-7.25(4H, m), 7.35-7.68(4H, m)      50      1.49-1.89(16H, m), 1.90-2.07(3H, m),              2.48-3.12(8H, m), 3.79-4.99(3H, m),              4.05(2H, t, J=7.2Hz), 6.89(2H, d, J=8.7Hz),              6.97-7.31(4H, m), 7.41(2H, d, J=8.7Hz)      51      1.27(3H, t, J=7.4Hz), 1.68-1.92(2H, m),              1.98-2.18(2H, m), 2.45-3.14(10H, m),              3.70-5.15(3H, m), 4.10(2H, t, J=6.1Hz),              6.91(2H, d, J=8.6Hz), 6.99-7.32(4H, m),              7.43(2H, d, J=8.6Hz)      52      1.18-1.37(3H, m), 1.50-2.02(2H, m),              2.32-3.35(11H, m), 4.45-4.51(9H, m),              4.78-5.09(1H, m), 6.39-6.60(2H, m),              6.94-7.35(5H, m)      53      1.65-1.97(2H, m), 2.49-3.10(11H, m),              3.78(3H, s), 3.85(2H, d, J=6.1Hz),              4.13-4.62(3H, m), 6.02(1H, t, J=6.1Hz),              6.14(1H, d, J=2.3Hz),              6.30(1H, dd, J=2.3, 8.5Hz), 6.84-7.35(6H, m)      54      1.62-2.05(2H, m), 2.48-3.28(8H, m),              3.47(1H, d, J=5.1Hz), 3.75-4.94(6H, m),              3.83(3H, s), 6.75-7.47(7H, m)      55      1.64-2.06(2H, m), 2.48-3.69(15H, m),              3.80(3H, m), 3.81-4.52(3H, m),              4.79-5.09(1H, m), 6.44-6.70(2H, m),              6.92-7.38(5H, m), 7.85-8.21(1H, m)      56      1.30(3H, t, J=7.1Hz), 1.71-1.92(2H, m),              2.47-3.11(8H, m), 3.79(3H, s),              3.91(2H, d, J=5.4Hz), 4.25(2H, q, J=7.1Hz),              4.31-4.61(3H, m), 5.91(1H, t, J=5.3Hz),              6.07(1H, d, J=2.3Hz),              6.26(1H, dd, J=2.3, 8.4Hz), 6.94-7.36(5H, m)      57      1.67-2.01(6H, m), 2.47-3.14(8H, m),              3.95-4.91(9H, m), 6.84-7.52(8H, m)      58      1.54-2.00(6H, m), 2.45-3.36(10H, m),              3.67(3H, s), 3.84-5.08(4H, m),              4.00(2H, t, J=5.9Hz), 6.89(2H, d, J=8.7Hz),              6.94-7.48(4H, m), 7.42(2H, d, J=8.7Hz)      59      1.55-2.00(6H, m), 2.45-3.48(10H, m),              3.76-5.10(3H, m), 3.99(2H, t, J=5.7Hz),              5.74-6.25(1H, m), 6.78-7.53(8H, m),              8.15(1H, s)      60      1.30(3H, t, J=7.1Hz), 1.67-1.90(2H, m),              2.49-3.26(10H, m), 3.81,(3H, s),              4.27-4.56(3H, m), 5.33-5.49(1H, m),              6.09-6.27(2H, m), 6.91-7.31(5H, m)      61      0.97(3H, t, J=7.5Hz), 1.55-2.01(4H, m),              2.09-2.35(2H, m), 2.41-5.13(18H, m),              6.90(2H, d, J=8.7Hz), 6.95-7.38(4H, m),              7.42(2H, d, J=8.7Hz)      62      1.51-2.02(8H, m), 2.48-3.20(10H, m),              3.72-5.08(3H, m), 4.01(2H, t, J=6.2Hz),              6.80-7.55(8H, m)      63      1.55-2.20(4H, m), 2.49-3.50(10H, m),              2.96(3H, m), 3.90-5.13(4H, m),              4.09(2H, t, J=5.7Hz), 6.90(2H, d, J=8.7Hz),              6.95-7.38(4H, m), 7.43(2H, d, J=8.7Hz)      64      1.60-2.15(5H, m), 2.47-3.18(10H, m),              3.82(2H, s), 3.95-5.11(3H, m),              4.08(3H, t, J=6.2Hz), 6.89(2H, d, J=8.5Hz),              6.95-7.50(9H, m), 7.42(2H, d, J=8.5Hz)      65      1.59-2.20(4H, m), 2.50-3.49(10H, m),              2.96(3H, s), 3.91-5.11(4H, m),              4.09(2H, t, J=5.7Hz), 6.90(2H, d, J=8.7Hz),              6.94-7.40(4H, m), 7.43(2H, d, J=8.7Hz)      66      1.60-2.10(4H, m), 2.45-3.49(13H, m),              3.80-5.01(7H, m), 6.88(2H, d, J=8.6Hz),              6.95-7.45(4H, m), 7.40(2H, d, J=8.6Hz)      67      1.63-2.15(4H, m), 1.99(3H, s), 2.49-3.20(8H, m)              3.35-3.60(2H, m), 3.90-5.10(3H, m),              4.06(2H, t, J=5.9Hz), 5.89(1H, brs),              6.89(2H, d, J=8.7Hz), 6.95-7.37(4H, m),              7.43(2H, d, J=8.7Hz)      68      1.60-2.32(4H, m), 2 41-3.27(8H, m),              3.71-5.15(5H, m), 4.07(2H, t, J=6.2Hz),              4.26(2H, t, J=6.2Hz), 6.96(2H, d, J=8.6Hz),              6.99-7.40(4H, m), 7.43(2H, d, J=8.6Hz)      69      0.86(3H, t, J=7.3Hz), 1.35-2.04(6H, m),              2.40(2H, t, J=7Hz), 2.50-3.17(10H, m),              3.57(2H, s), 3.90-5.05(3H, m),              4.00(2H, t, J=6.5Hz), 6.85(2H, d, J=8.8Hz),              6.94-7.38(9H, m), 7.42(2H, d, J=8.8Hz)      70      0.99-1.23(3H, m), 1.54-2.00(2H, m),              2.35-3.40(13H, m), 3.52-3.77(1H, m),              3.80(3H, s), 4.15-4.52(1H, m),              4.83-5.04(1H, m), 6.49-6.57(2H, m),              6.90-7.35(4H, m)      71      1.50-2.12(6H, m), 2.03(3H, m),              2.45-3.44(10H, m), 3.88(2H, d, J=5.1Hz),              3.98(2H, t, J=6.0Hz), 4.01-5.05(3H, m),              6.50-7.52(10H, m)      72      1.45-2.01(8H, m), 2.06(3H, s),              2.48-3.25(8H, m), 3.70-5.12(3H, m),              3.99(2H, t, J=6.3Hz), 4.10(2H, t, J=6.3Hz),              6.89(2H, d, J=8.8Hz), 6.97-7.35(4H, m),              7.43(2H, d, J=8.8Hz)      73      1.40-2.02(8H, m), 2.48-3.15(8H, m),              3.60-5.12(3H, m), 3.72(2H, t, J=7.0Hz),              3.97(2H, t, J=6.3Hz), 6.87(2H, d, J=8.7Hz),              6.92-7.32(4H, m), 7.41(2H, d, J=8.7Hz),              7.61-7.93(4H, m)      74      1.35-2.02(10H, m), 2.47-3.25(10H, m),              3.71-5.16(3H, m), 3.99(2H, t, J=6.4Hz),              6.89(2H, d, J=8.7Hz), 6.93-7.35(4H, m),              7.42(2H, d, J=8.7Hz)      75      1.01-5.60(20H, m), 3.82(3H, s),              6.55-7.60(12H, m)      76      1.52-5.51(17H, m), 3.83(3H, s),              6.75-7.55(12H, m)      77      1.50-5.52(20H, m), 3.82(3H, s),              6.69-7.55(12H, m), 9.20-9.75(1H, m)      78      1.09-5.45(25H, m), 6.77-7.48(12H, m)      79      1.65-1.97(2H, m), 2.10-2.30(2H, m),              2.48-3.01(8H, 3.82-4.78(7H, m),              6.62-6.93(4H, 7.11(1H, dd, J=6.2, 7.3Hz),              7.38(2H, d, J=8.5Hz), 7.66-7.86(4H, m)      80      1.55-2.10(4H, m), 2.43-3.18(10H, m),              3.74-5.18(5H, m), 6.65-7.00(4H, m),              7.10(1H, dd, J=6.4, 7.3Hz),              7.41(2H, d, J=8.7Hz)      81      1.60-1.90(2H, m), 1.98(3H, s),              1.90-2.10(2H, m), 2.43-3.10(8H, m),              3.45(2H, q, J=6.4Hz), 4.05(2H, t, J=5.9Hz),              3.82-5.04(3H, m), 5.92(1H, brs),              6.65-6.97(4H, m), 7.11(1H, dd, J=6.4, 7.3Hz),              7.43(2H, d, J=8.7Hz)      82      1.25(3H, t, J=7.5Hz), 1.64-1.82(2H, m),              1.91(1H, brs), 2.35-2.87(10H, m),              3.15-3.35(2H, m), 4.16-4.50(1H, m),              6.85(1H, d, J=7.7Hz), 7.00(1H, s),              7.10(1H, d, J=7.7Hz)      83      1.26(3H, t, J=7.5Hz), 1.58-1.98(2H, m),              2.45-3.22(10H, m), 3.58-3.98(7H, m),              4.23-4.61(1H, m), 4.87-5.05(1H, m),              6.40-6.57(2H, m), 6.80-7.38(3H, m)      84      1.62-1.95(2H, m), 2.50-2.93(9H, m),              3.15-3.50(2H, m), 3.84(3H, s),              4.15-4.48(1H, m), 6.50-6.60(1H, m),              6.70-6.82(1H, m), 7.06(1H, d, J=8.2Hz)      85      1.55-1.98(2H, m), 2.44-3.25(8H, m),              3.60-4.10(10H, m), 4.20-4.75(1H, m),              4.86-5.05(1H, m), 6.44-6.85(4H, m),              7.07(1H, d, J=8.2Hz), 7.17-7.36(1H, m)      86      1.54-1.92(2H, m), 2.32-3.22(8H, m),              3.50-3.90(7H, m), 4.23-4.71(1H, m),              4.82-5.00(1H, m), 6.34-6.60(2H, m),              6.95-7.72(5H, m), 7.90(2H, d, J=7.0Hz),              8.40-8.65(1H, m)      87      1.50-1.93(2H, m), 2.34-3.20(8H, m),              3.30-4.15(9H, m), 4.22-4.75(1H, m),              4.85-5.03(1H, m), 6.42-6.63(4H, m),              6.82-7.33(2H, m)      88      1.60-2.02(2H, m), 2.62-3.41(4H, m),              3.73-4.26(1H, m), 4.50-5.72(2H, m),              6.64(1H, d, J=9.4Hz), 7.15-7.70(10H, m)      89      1.55-1.96(2H, m), 2.72-3.30(4H, m),              3.84(3H, s), 3.82-5.55(3H, m),              6.65(1H, d, J=9.4Hz), 6.93(2H, d, J=8.7Hz),              7.23(1H, t, J=7.6Hz), 7.48-7.75(6H, m)      90      1.55-1.95(2H, m), 2.63-3.34(4H, m),              3.66-4.00(7H, m), 4.95-5.16(1H, m),              6.42-6.77(3H, m), 7.13-7.40(2H, m),              7.45-7.86(4H, m)      91      1.62-2.03(3H, m), 2.55-3.03(4H, m),              3.14-3.50(2H, m), 4.68-5.85(1H, br),              6.65(1H, d, J=9.4Hz), 7.19(1H, t, J=7.4Hz)      92      1.55-1.98(2H, m), 2.38-3.26(8H, m),              3.57-4.00(7H, m), 4.24-4.71(1H, m),              4.85-5.07(1H, m), 6.50-6.61(2H, m),              6.83-7.39(4H, m)      93      1.60-2.05(3H, m), 2.31-3.00(8H, m),              3.10-3.48(2H, m), 4.21-4.52(1H, m),              6.76-7.38(3H, m)      94      2.76(3H, t, J=8.1Hz), 3.0(3H, t, J=8Hz),              3.48(3H, s), 3.75(3H, s),              6.19(1H, dd, J=3.1, 6Hz), 6.78(2H, d, J=8.3Hz),              6.9-7.2(7H, m), 7.43(2H, d, J=8.4Hz)      95      1.57-1.95(2H, m), 2.50(3H, s),              2.45-3.25(7H, m), 3.57-4.00(4H, m),              4.15-4.77(1H, m), 4.88-5.07(1H, m),              6.63-7.36(6H, m)      96      1.73-1.95(2H, m), 2.49-3.11(8H, m),              3.84(3H, s), 4.24-4.58(3H, m),              5.21(2H, s), 6.57(1H, dd, J=2.5, 8.5Hz),              6.96-7.52(10H, m), 7.87(1H, d, J=2.5Hz),              8.81(1H, s)      97      1.54-1.72(1H, m), 1.77-1.92(1H, m),              2.40-3.23(8H, m), 3.58-3.73(1H, m), 3.73-3.95              (6H, m), 4.20-4.77(1H, m), 4.88-5.07(1H, m),              6.43-6.60(2H, m), 6.65-7.00(2H, m),              7.05-7.37(2H, m)      98      1.55-1.93(2H, m), 2.30(3H, s),              2.40-3.24(8H, m), 3.56-3.72(1H, m),              3.73-3.85(6H, m), 4.27-4.73(1H, m),              4.85-5.02(1H, m), 6.41-6.57(2H, m),              6.90-7.37(4H, m)      99      1.58-2.00(2H, m), 2.35(3H, s),              2.32-3.14(8H, m), 3.27-3.48(1H, m),              3.53-4.00(7H, m), 4.78-5.01(1H, m),              6.37-6.64(2H, m), 6.87-7.48(4H, m)     100      1.57-1.97(2H, m), 2.37(3H, s),              2.43-3.26(8H, m), 3.48-3.98(7H, m),              4.21-4.63(1H, m), 4.84-5.07(1H, m),              6.42-6.60(2H, m), 6.78-7.37(4H, m)     101      1.40(3H, t, J=7.1Hz), 1.55-2.09(2H, m),              2.43-3.34(8H, m), 3.66-4.07(1H, m),              4.25-4.58(1H, m), 4.39(2H, q, J=7.1Hz),              4.75-5.12(1H, m), 6.96-7.74(6H, m),              8.01-8.23(2H, m)     102      2.3-2.7(4H, br), 2.8(2H, t, J=8Hz),              3.1(2H, t, J=8Hz), 3.4-3.9(4H, m),              3.55(2H, s), 6.36(1H, dd, J=2.2, 6.9Hz),              6.9-7.1(2H, m), 7.1-7.4(8H, m),              7.54(2H, d, J=8.4Hz)     103      1.60-2.08(2H, m), 2.45-3.10(8H, m),              3.35(3H, s), 3.62-4.05(1H, br),              4.34(1H, m), 4.60-5.07(1H, br),              5.16(2H, s), 6.76-7.53(13H, m)     104      1.82(2H, m), 2.54-3.32(8H, m),              3.77(1H, brs), 4.35(1H, m),              4.89(1H, brs), 7.00-7.30(4H, m),              7.59-7.67(1H, m), 7.80-7.84(1H, m),              8.27-8.33(2H, m)     105      1.68-2.01(2H, m), 2.50-3.09(11H, m),              4.19-4.73(3H, m), 4.88-5.33(1H, m),              6.60-6.75(2H, m), 4.96-7.39(6H, m)     106      1.60-2.03(2H, m), 2.45-3.32(8H, m),              3.67-4.07(1H, m), 4.15-4.44(1H, m),              4.61-5.04(1H, m), 6.96-7.68(7H, m)     107      1.51-2.08(2H, m), 2.42-3.67(9H, m),              4.15-5.09(2H, m), 6.90-7.62(7H, m)     108      0.94(3H, t, J=7.3Hz), 1.50-1.97(4H, m),              2.50-3.20(10H, m), 3.74-4.20(1H, br),              4.41(1H, m), 4.50-5.08(1H, br),              6.98-7.34(6H, m), 7.38(2H, d, J=8.1Hz)     109      1.85(2H, m), 2.55-3.30(8H, m),              3.78-4.38(1H, br), 4.41(1H, m),              4.66-5.17(1H, br), 6.99-7.66(13H, m)     110      1.84(2H, m), 2.55-3.10(8H, m),              4.00-5.00(2H, m), 4.40(1H, m),              4.57(2H, d, J=5.3Hz), 5.31(1H, d, J=10.5Hz),              5.42(1H, d, J=16.6Hz),              6.06(1H, ddt, J=16.6, 10.5, 5.3Hz),              6.93(2H, d, J=8.7Hz), 6.99-7.32(4H, m),              7.43(2H, d, J=8.7Hz)     111      1.82(2H, m), 2.51-3.12(8H, m),              3.43(2H, d, J=6.8Hz), 4.12-4.70(2H, m),              4.43(1H, m), 4.58(2H, d, J=5.0Hz),              5.06(1H, d, J=10.0Hz), 5.08(1H, d, J=17.0Hz),              5.29(1H, d, J=9.0Hz), 5.43(1H, d, J=18.9Hz),              5.92-6.16(2H, m), 6.84(1H, d, J=8.5Hz),              7.00-7.37(6H, m)     112      1.6-2.1(3H, m), 2.4-2.7(2H, m),              2.7-3.2(4H, m), 3.4-4.2(3H, m),              3.8(6H, s), 4.7-5.0(1H, br),              6.4-6.6(2H, m), 6.9-7.4(5H, m)     113      1.66-1.97(2H, m), 2.44-3.10(8H, m),              3.90-5.00(2H, m), 4.39(1H, m),              6.00(2H, s), 6.83(1H, d, J=8.2Hz),              6.96-7.32(6H, m)     114      1.83(2H, m), 2.31(3H, s), 2.48-3.17(8H, m),              3.82(3H, s), 4.13-4.63(2H, m),              4.70-5.02(1H, m), 6.67-6.88(2H, m),              6.97-7.49(5H, m)     115      1.70-1.92(2H, m), 2.47-3.08(11H, m),              3.82(3H, s), 4.26-4.61(3H, m),              5.55(1H, brs), 6.12-6.29(2H, m),              6.95-7.36.(5H, m)     116      1.42(3H, t, J=6.9Hz), 1.64-1.90(2H, m),              2.44-3.17(8H, m), 4.05(2H, q, J=6.9Hz),              3.90-5.00(3H, m), 6.65-6.98(4H, m),              7.03-7.17(1H, m), 7.41(2H, d, J=8.7Hz)     117      1.64-2.10(4H, m), 2.97-3.18(8H, m),              2.92(2H, t, J=6.8Hz), 4.08(2H, t, J=6.1Hz),              4.10-5.15(3H, m), 6.82-7.58(8H, m)              MS(m/e): 407(m.sup.+), 333, 260, 229, 121, 82     118      1.62-1.95(2H, m), 2.07-2.33(2H, m),              2.43-3.16(8H, m), 3.92(2H, t, J=6.8Hz),              4.06(2H, t, J=6.1Hz), 3.95-5.05(3H, m),              6.80(2H, d, J=8.7Hz), 6.95-7.39(4H, m),              7.38(2H, d, J=8.7Hz), 7.65-8.00(4H, m)     119      2.76(2H, t, J=8.1Hz), 3.02(2H, t, J=7.8Hz),              3.72(3H, s), 5.10(2H, s),              6.17(1H, dd, J=2.6, 6.5Hz),              6.68(2H, d, J=9.0Hz), 6.85(2H, d, J=8.8Hz),              6.9-7.4(10H, m), 7.46(2H, d, J=8.5Hz)     120      2.76(2H, t, J=8.1), 3.02(2H, t, J=7.9Hz),              3.75(3H, s), 4.50(2H, d, J=6Hz),              5.20(1H, d, J=1.62Hz), 5.19(1H, d, J=11.0Hz),              5.9-6.1(1H, m), 6.18(1H, dd, J=2.6, 6.5Hz),              6.76(2H, d, J=8.9Hz), 6.9-7.3(7H, m),              7.45(2H, d, J=8.3Hz)     121      1.64-1.96(2H, m), 2.15-2.87(2H, m),              2.49-3.20(8H, m), 3.01(3H, s),              4.02-5.03(3H, m), 4.12(2H, t, J=5.9Hz),              4.53(2H, t, J=6.1Hz), 6.91(2H, d, J=8.7Hz),              6.95-7.46(4H, m), 7.44(2H, d, J=8.7Hz)     122      1.55-3.26(14H, m), 2.72(6H, s),              3.90-5.18(3H, m), 4.05(2H, t, J=5.7Hz),              6.90(2H, d, J=8.7Hz), 6.93-7.38(4H, m),              7.43(2H, d, J=8.7Hz)     123      0.91(3H, t, J=5.8Hz), 1.42-3.31(21H, m),              2.33(3H, s), 3.88-5.15(3H, m),              4.05(2H, t, J=5Hz), 6.91(2H, d, J=7Hz),              6.95-7.38(4H, m), 7.42(2H, d, J=7Hz)     124      1.65-5.12(22H, m), 6.67-7.60(13H, m)     125      1.65-1.99(2H, m), 2.07(2H, quint, J=6.2Hz),              2.49-3.24(8H, m), 3.62(2H, t, J=6.2Hz),              3.87-4.93(5H, m), 4.10(2H, t, J=6.2Hz),              5.11-5.38(2H, m), 5.80-6.07(1H, m),              6.80-7.53(8H, m)     126      1.02(3H, t, J=7.3Hz), 1.60-2.07(4H, m),              2.47-3.18(10H, m), 3.80(3H, s),              4.30-4.58(3H, m), 5.53(1H, t, J=5.2Hz),              6.07-6.28(2H, m), 6.94-7.34(5H, m)     127      1.64-1.92(2H, m), 2.28(2H, quint, J=6.1Hz),              2.45-3.27(8H, m), 4.02-5.22(3H, m),              4.16(2H, t, J=6.1Hz), 4.53(2H, t, J=6.1Hz),              6.83-7.69(11H, m), 7.98-8.18(2H, m)     128      1.69-1.97(2H, m), 2.06(2H, quint, J=6.2Hz),              2.48-3.16(8H, m), 3.36(3H, s),              3.56(2H, t, J=6.2Hz), 4.09(2H, t, J=6.2Hz),              4.12-5.04(3H, m), 6.91(2H, t, J=8.7Hz),              6.94-7.35(4H, m), 7.43(2H, d, J=8.7Hz)     129      1.28(3H, t, J=7.1Hz), 1.83(2H, m),              2.15(2H, quint, J=6.7Hz), 2.47(2H, t, J=6.7Hz),              2.50-3.20(8H, m), 3.60-5.10(2H, m),              4.02(2H, s), 4.05(2H, t, J=6.7Hz),              4.21(2H, q, J=7.1Hz), 4.39(1H, m),              6.12(1H, brs), 6.91(2H, d, J=8.6Hz),              6.99-7.29(4H, m), 7.42(2H, d, J=8.6Hz)     130      1.87(2H, m), 2.50-3.43(8H, m),              3.94(1H, m), 4.38(1H, m), 4.96(1H, m),              6.99-7.30(4H, m), 7.58-7.65(1H, m),              7.75-7.98(2H, m), 8.12-8.16(1H, m),              8.31(1H, m), 9.01(1H, m)     131      1.73(6H, m), 1.82(2H, m), 2.04(9H, m),              2.43-3.00(8H, m), 4.46(1H, m), 4.67(1H, m),              4.73(1H, m), 6.98-7.30(4H, m)     132      1.65-2.28(7H, m), 2.44-3.20(11H, m),              3.42-5.11(7H, m), 6.83-7.60(8H, m)     133      1.40-1.90(2H, m), 2.30-2.95(8H, m),              3.90(3H, s), 3.98(2H, m),              4.32(1H, m), 6.90-7.27(6H, m), 7.73(2H, m)     134      1.55-2.05(2H, m), 2.54-3.33(8H, m),              4.05-4.24(1H, m), 4.47-4.65(1H, m),              4.93-5.10(1H, m), 6.98-7.31(4H, m),              7.64(1H, m), 7.71-7.80(2H, m), 7.86(1H, m),              8.11(1H, d, J=8.4Hz), 8.28(1H, d, J=8.4Hz)     135      1.56-1.86(1H, m), 1.86-2.30(1H, m),              2.44-3.35(8H, m), 3.60-3.86(1H, m),              4.12-4.62(1H, m), 4.91-5.20(1H, m),              6.63-7.78(9H, m)     136      1.08(9H, s), 1.80(2H, m), 2.32(2H, s), 2.45-2.76              (5H, m), 2.76-2.92(2H, m), 3.05-3.18(1H, m),              4.03-4.18(1H, m), 4.40(1H, m),              4.78-4.98(1H, m), 6.97-7.28(4H, m)     137      1.30(3H, t, J=7.1Hz), 1.84(2H, m),              2.50-3.22(8H, m), 3.90(1H, t, J=5.4Hz),              3.43-5.20(2H, m), 4.13(2H, d, J=5.4Hz),              4.24(2H, q, J=7.1Hz), 4.57(2H, s),              4.38(1H, m), 6.97(2H, d, J=8.7Hz),              7.03-7.32(4H, m), 7.47(2H, d, J=8.7Hz)     138      1.75(2H, m), 2.51-3.31(8H, m),              3.80-5.28(2H, m), 4.37(1H, m),              4.64(2H, s), 6.90-7.67(13H, m)     139      1.83(2H, m), 2.54-3.23(8H, m),              2.94(3H, s), 3.09(3H, s),              3.76-5.17(2H, m), 4.39(1H, m),              4.73(2H, s), 6.97(2H, d, J=8.6Hz),              7.02-7.27(4H, m), 7.43(2H, d, J=8.6Hz)     140      1.26(3H, t, J=7.1Hz), 1.83(2H, m),              2.12(2H, quint, J=6.2Hz), 2.40-3.20(10H, m),              3.40-5.10(2H, m), 4.04(2H, t, J=6.2Hz),              4.15(2H, q, J=7.1Hz), 4.39(1H, m),              6.90(2H, d, J=8.6Hz), 6.98-7.28(4H, m),              7.43(2H, d, J=8.6Hz)     141      1.54-1.98(2H, m), 2.40-3.22(9H, m),              2.95(6H, s), 3.58-3.90(7H, m),              4.85-5.06(1H, m), 6.33-6.62(4H, m),              6.70(1H, d, J=8.2Hz), 7.12-7.30(1H, m)     142      1.27(3H, d, J=6.8Hz), 1.55-1.95(2H, m),              2.28-3.24(7H, m), 3.55-3.97(7H, m),              4.27-4.73(1H, m), 4.75-5.07(1H, m),              6.38-6.60(2H, m), 6.97-7.38(5H, m)     143      1.67-3.23(12H, m), 2.06(3H, s),              3.94-5.15(3H, m), 4.08(2H, t, J=6.2Hz),              4.26(2H, t, J=6.2Hz), 6.77-7.75(8H, m)     144      1.54-2.23(5H, m), 2.51-3.20(8H, m),              3.77-5.08(5H, m), 4.15(2H, t, J=6Hz),              6.83-7.59(8H, m)     145      1.31(3H, t, J=7.1Hz), 1.83(2H, m),              2.54-3.26(8H, m), 3.70-5.20(2H, m),              4.30(2H, q, J=7.1Hz), 4.38(1H, m), 4.65(2H, s),              6.93(2H, d, J=8.7Hz), 6.99-7.36(4H, m),              7.44(2H, d, J=8.7Hz)     146      1.6-2.1(3H, m), 2.4-2.6(2H, m), 2.5(3H, s),              2.6-3.2(4H, m), 3.4-4.1(6H, m),              4.8-5.0(1H, br), 6.6-7.4(7H, m)     147      1.55-1.93(2H, m), 2.30-3.24(8H, m),              3.56-4.05(10H, m), 4.27-4.72(1H, m),              4.84-5.07(1H, m), 6.40-6.60(2H, m),              6.64-6.82(2H, m), 6.93-7.38(2H, m)     148      1.80(2H, m), 2.31(3H, s), 2.52-3.25(8H, m),              3.68-4.20(1H, br), 4.34(1H, m),              4.65-5.13(1H, br), 6.88-7.52(8H, m)     149      1.56-2.00(2H, m), 2.30(6H, s),              2.50-3.15(8H, m), 3.20-3.90(1H, m),              4.27(1H, m), 4.90(1H, m),              6.95-7.33(7H, m)     150      1.70-2.00(2H, m), 2.55-3.15(8H, m),              4.33(1H, m), 4.47(1H, m), 4.54(1H, m),              6.36-6.49(2H, m), 7.02-7.35(5H, m)     151      1.59-2.11(2H, m), 2.48-3.33(8H, m),              3.70-5.15(3H, m), 5.58-6.60(2H, m),              6.97-8.05(8H, m)     152      1.56-3.35(13H, m), 3.60-5.08(3H, m),              6.75-7.98(8H, m)     153      1.31-1.78(5H, m), 2.32-3.28(8H, m), 3.68(1H, m),              3.81(3H, s), 4.06(2H, m), 4.43(1H, m),              4.96(1H, m), 6.49-6.62(2H, m),              6.97-7.44(5H, m)     154      1.53-1.90(2H, m), 2.35-3.27(8H, m),              3.60-3.77(1H, m), 3.81(3H, s),              4.29-4.60(1H, br), 4.58(2H, m),              4.88-5.06(1H, m), 5.18-5.51(2H, m),              6.08(1H, m), 6.42-6.60(2H, m),              6.93-7.48(5H, m)     155      2.78(3H, t, J=8Hz), 3.04(3H, t, J=8Hz),              3.50(3H, s), 3.59(3H, s), 3.76(3H, s),              6.0-6.1(1H, br), 6.2(1H, brs),              6.41(1H, dd, J=2.3, 8.4Hz), 6.9-7.1(4H, m),              7.1-7.3(4H, m)     156      1.66-2.03(2H, m), 2.14(2H, m),              2.44(2H, t, J=7.2Hz), 2.51-3.32(8H, m),              3.70-5.30(2H, m), 4.04(2H, t, J=6.0Hz),              4.38(1H, m), 5.75(1H, brs), 5.90(1H, brs),              6.90(2H, d, J=8.6Hz), 6.99-7.29(4H, m),              7.42(2H, d, J=8.6Hz)     157      1.55-2.10(2H, m), 2.22-3.36(8H, m),              3.78-4.20(1H, m), 4.23-4.56(1H, m),              4.70-5.18(1H, m), 6.95-7.34(4H, m),              7.46(1H, dd, J=8.3, 4.2Hz),              7.67(1H, dd, J=8.3, 1.3Hz),              7.90(1H, d, J=8.3Hz), 8.20(2H, m),              8.96(1H, dd, J=4.2, 1.3Hz)     158      1.58-2.31(4H, m), 2.44-3.30(8H, m),              3.60-4.50(6H, m), 3.81(3H, s),              4.70-5.15(1H, m), 6.43-6.60(2H, m),              6.99-7.33(5H, m)     159      1.29(3H, t, J=7.1Hz), 1.58-1.98(2H, m),              2.53-3.37(8H, m), 3.80(3H, s),              4.21(2H, q, J=7.1Hz), 4.22-4.47(1H, m),              4.62(2H, s), 4.63-4.80(1H, m), 4.87-5.07(1H, m),              6.28-6.37(1H, m), 6.52-6.66(1H, m),              6.95-7.46(5H, m)     160      1.46-2.12(2H, m), 2.45-3.22(8H, m),              3.36-3.55(1H, m), 4.22-4.53(1H, m),              5.02-5.17(1H, m), 6.98-7.74(7H, m),              8.03-8.26(2H, m), 8.94-9.05(1H, m)     161      1.26(3H, t, J=7.1Hz), 1.63-2.00(6H, m),              2.32-2.44(2H, m), 2.54-3.03(8H, m),              3.75-5.03(2H, m), 3.95-4.09(2H, m),              4.14(2H, q, J=7.1Hz), 4.40(1H, m),              6.90(2H, d, J=8.7Hz), 6.98-7.27(4H, m),              7.43(2H, d, J=8.7Hz)     162      1.42-1.62(2H, m), 1.62-1.93(6H, m),              2.36(2H, t, J=7.1Hz), 2.45-3.12(8H, m),              3.67(3H, s), 3.74-5.03(2H, m),              3.98(2H, t, J=6.3Hz), 4.39(1H, m),              6.90(2H, d, J=8.7Hz), 6.99-7.28(4H, m),              7.43(2H, d, J=8.7Hz)     163      1.63-2.10(6H, m), 2.33(2H, m),              2.46-3.18(8H, m), 3.50-5.00(2H, m),              3.89(2H, d, J=4.8Hz), 4.00(2H, m),              4.37(1H, m), 5.76(1H, brs), 6.50(1H, brs),              6.74(1H, brs), 6.89(2H, d, J=8.6Hz),              6.99-7.27(4H, m), 7.41(2H, d, J=8.6Hz)     164      1.28(3H, t, J=7.1Hz), 1.83(6H, m),              2.17(2H, m), 2.43-3.18(8H, m),              3.55-5.00(2H, m), 3.98(2H, m), 3.99(2H, d, J=5.1              Hz), 4.20(2H, q, J=7.1Hz), 4.37(1H, m),              6.66(1H, brs), 6.89(2H, d, J=8.6Hz),              6.99-7.32(4H, m), 7.42(2H, d, J=8.6Hz)     165      1.41-2.10(8H, m), 2.26(2H, t, J=7.3Hz),              2.54-3.24(8H, m), 3.80-5.10(2H, m),              3.99(2H, t, J=6.3Hz), 4.39(1H, m),              5.22-5.86(2H, m), 6.89(2H, d, J=8.7Hz),              6.99-7.29(4H, m), 7.42(2H, d, J=8.7Hz)     166      1.48-1.62(2H, m), 1.62-2.17(6H, m),              2.27(2H, t, J=7.3Hz), 2.54-3.30(8H, m),              3.30-5.10(2H, m), 3.91(2H, d, J=5.0Hz),              3.98(2H, t, J=6.3Hz), 4.37(1H, m),              5.75(1H, brs), 6.51(1H, brs), 6.66(1H, brs),              6.89(2H, d, J=8.7Hz), 6.99-7.27(4H, m),              7.41(2H, d, J=8.7Hz)     .sup.   166A              1.28(3H, t, J=7.1Hz), 1.46-1.63(2H, m),              1.63-1.96(6H, m), 2.28(2H, t, J=7.3Hz),              2.54-3.12(8H, m), 3.62-5.07(2H, m),              3.98(2H, t, J=6.4Hz), 4.01(2H, d, J=5.3Hz),              4.20(2H, q, J=7.1Hz), 4.48(1H, m),              6.45(1H, brs), 6.89(2H, d, J=8.7Hz) ,              6.99-7.31(4H, m), 7.42(2H, d, J=8.7Hz)     167      1.57-1.94(2H, m), 2.02-2.35(2H, m),              2.06(3H, s), 2.45-3.24(8H, m),              3.64(1H, m), 3.82(3H, s), 3.98-4.50(5H, m),              4.85-5.06(1H, m), 6.38-6.63(2H, m),              6.97-7.33(5H, m)     168      1.67(1H, m), 1.75-1.94(1H, m),              2.00-2.37(2H, m), 2.45-3.26(8H, m),              3.56-3.80(1H, m), 3.81(3H, s),              3.94-4.47(5H, m), 4.66-5.27(3H, m),              6.44-6.55(2H, m), 6.98-7.32(5H, m)     169      1.55-1.77(1H, m), 1.77-1.94(1H, m),              1.94-2.33(2H, m), 2.33-3.24(8H, m),              3.35(3H, s), 3.42-3.77(3H, m), 3.81(3H, s),              3.95-4.27(2H, m), 4.40(1H, m),              4.87-5.07(1H, m), 6.42-6.62(2H, m),              6.98-7.32(5H, m)     170      1.53-1.77(1H, m), 1.77-1.98(1H, m),              2.32-3.33(8H, m), 3.43(3H, s),              3.56-3.99(3H, m), 3.81(3H, s),              3.99-4.30(2H, m), 4.40(1H, m),              4.85-5.06(1H, m), 6.49-6.66(2H, m),              6.97-7.43(5H, m)     171      1.62-1.82(1H, m), 1.82-2.02(1H, m),              2.03-2.40(2H, m), 2.40-3.26(10H, m),              3.68-3.90(1H, m), 3.81(3H, s), 3.97(1H, m),              4.02-4.26(2H, m), 4.36-5.10(1H, m),              6.43-6.57(2H, m), 7.00-7.29(5H, m)     172      1.26-1.98(12H, m), 2.20(2H, t, J=7.5Hz),              2.53-3.27(8H, m), 3.77-5.05(2H, m),              3.97(2H, t, J=6.4Hz), 4.37(1H, m),              6.01(1H, brs), 6.05(1H, brs),              6.90(2H, d, J=8.6Hz), 6.99-7.29(4H, m),              7.42(2H, d, J=8.6Hz)     173      1.26(3H, t, J=7.1Hz), 1.54-1.75(1H, m),              1.75-1.96(1H, m), 2.03-2.33(2H, m),              2.44-3.24(10H, m), 3.57-3.78(1H, m),              3.80(3H, s), 4.01(2H, t, J=6.3Hz),              4.14(2H, q, J=7.1Hz), 4.39(1H, m),              4.82-5.04(1H, m), 6.40-6.59(2H, m),              6.98-7.33(5H, m)     174      1.10-2.06(12H, m), 2.23(2H, t, J=7.5Hz),              2.42-3.24(8H, m), 3.67-5.15(2H, m),              3.90(2H, d, J=5.2Hz), 3.97(2H, t, J=6.4Hz),              4.37(1H, m), 6.09(1H, brs),              6.90(2H, d, J=8.6Hz), 6.97-7.30(4H, m),              7.41(2H, d, J=8.6Hz)     175      1.27(3H, t, J=7.1Hz), 1.39(3H, d, J=7.2Hz),              1.63-1.95(2H, m), 2.14(2H, quint, J=6.5Hz),              2.43(2H, t, J=6.5Hz), 2.54-3.10(8H, m),              3.80-5.15(2H, m), 4.04(2H, t, J=6.5Hz),              4.19(2H, q, J=7.1Hz), 4.39(1H, m),              4.57(1H, quint, J=7.2Hz), 6.29(1H, d, J=7.2Hz),              6.90(2H, d, J=8.7Hz), 6.99-7.29(4H, m),              7.42(2H, d, J=8.7Hz)     176      1.18-1.54(6H, m), 1.54-1.93(6H, m),              2.32(2H, t, J=7.4Hz), 2.54-3.10(8H, m),              3.67(3H, s), 3.80-5.05(2H, m),              3.97(2H, t, J=6.5Hz), 4.40(1H, m),              6.70(2H, d, J=8.6Hz), 6.99-7.27(4H, m),              7.43(2H, d, J=8.6Hz)     177      1.62-1.96(2H, m), 2.52-3.18(8H, m),              3.68-4.42(6H, m), 3.81(3H, s),              4.80-5.05(1H, m), 6.47-6.64(2H, m),              6.99-7.29(5H, m)     178      1.54-1.93(2H, m), 2.04(3H, s),              2.27-3.28(8H, m), 3.56-3.80(1H, m),              3.81(3H, s), 4.00-4.73(5H, m),              4.83-5.05(1H, m), 6.49-6.65(2H, m),              6.98-7.36(4H, m)     179      1.52-1.98(2H, m), 2.12(2H, quint, J=6.5Hz),              2.45(2H, t, J=6.5Hz), 2.54-3.24(8H, m),              3.65-5.18(2H, m), 3.89(2H, d, J=5.2Hz),              4.02(2H, t, J=6.5Hz), 4.36(1H, m),              6.00(1H, brs), 6.61(1H, brs),              6.89(2H, d, J=8.6Hz), 6.99-7.29(5H, m),              7.40(2H, d, J=8.6Hz)     180      1.57-1.94(2H, m), 2.12(2H, quint, J=6.6Hz),              2.43(2H, t, J=6.6Hz), 2.54-3.14(8H, m),              3.28(1H, m), 3.76(3H, s), 4.00(2H, d, J=3.8Hz),              4.01(2H, t, J=6.6Hz), 4.10-5.00(1H, m),              4.37(1H, m), 4.65(1H, dt, J=7.6, 3.8Hz),              6.74(1H, d, J=7.6Hz), 6.91(2H, d, J=8.7Hz),              6.99-7.29(4H, m), 7.42(2H, d, J=8.7Hz)     181      1.22-1.94(18H, m), 2.31(2H, t, J=7.5Hz),              2.42-3.17(8H, m), 3.66(3H, s),              3.80-5.10(2H, m), 3.97(2H, t, J=6.5Hz),              4.40(1H, m), 6.90(2H, d, J=8.6Hz),              6.99-7.28(4H, m), 7.43(2H, d, J=8.6Hz)     182      0.9-1.4(3H, s), 1.5-1.8(1H, m),              2.3-2.7(3H, m), 2.8-3.3(4H, m),              3.3-4.0(8H, m), 4.2-4.5(1H, m),              4.6-4.9(1H, br), 6.4-6.6(2H, m),              7.0-7.4(5H, m)     183      1.12(3H, d, J=6.9Hz), 1.6-1.8(1H, m),              2.4-2.7(3H, m), 2.8-2.9(2H, m),              3.00(6H, s), 2.9-3.4(3H, m),              4.1-4.5(3H, m), 6.68(2H, d, J=8.8Hz),              7.0-7.3(4H, m), 7.40(2H, d, J=8.8Hz)     184      1.6-1.8(6H, m), 2.1-2.3(3H, br),              2.3-2.4(6H, br), 2.7-2.9(2H, m),              2.92(3H, s), 3.0-3.2(2H, m),              6.3-6.5(1H, m), 6.9-7.1(2H, m),              7.2-7.3(1H, m), 7.25(2H, d, J=8.5Hz),              7.56(2H, d, J=8.5Hz)     185      2.1-2.3(1H, m), 2.5-2.9(5H, m),              3.3-4.2(10H, m), 5.0-5.2(1H, m),              6.4-6.6(2H, m), 7.0-7.2(2H, m)     186      2.1-2.3(1H, m), 2.5-2.9(5H, m),              2.99(6H, s), 3.6-4.3(4H, m),              4.8-5.0(1H, br), 6.6-6.7(2H, m)     187      2.1-2.4(1H, m), 2.5-3.0(8H, m),              3.3-4.2(7H, m), 5.0-5.2(1H, m),              6.7-7.1(4H, m), 7.1-7.3(3H, m)     188      1.22(3H, d, J=7.1Hz), 1.5-1.7(1H, m),              2.3-2.5(1H, m), 2.5-3.3(9H, m),              4.1-4.3(1H, m), 6.9-7.1(1H, m),              7.1-7.3(3H, m)     189      1.6-2.0(3H, m), 2.5-2.6(8H, m),              3.6-3.9(2H, m), 4.0-4.3(1H, m),              6.9-7.1(1H, m), 7.1-7.3(3H, m)     190      2.1-2.4(2H, m), 2.5-2.7(2H, m),              2.7-3.1(3H, m), 3.1-3.3(1H, m),              3.3-3.6(2H, m), 3.9(1H, s),              4.6-4.8(1H, m), 7.0-7.3(4H, m)     191      1.65-1.97(2H, m), 2.40-2.92(9H, m),              3.15-3.34(2H, m), 3.78(3H, s),              4.25-4.49(1H, m), 6.67-6.72(2H, m),              7.16(1H, d, J=8.9Hz)     192      1.55-1.85(3H, m), 2.30(3H, s),              2.36-2.90(8H, m), 3.15-3.32(2H, m),              4.23-4.48(1H, m), 6.90-7.06(2H, m),              7.11(1H, d, J=8.1Hz)     193      1.63-1.95(3H, m), 2.36(3H, s),              2.43-2.90(8H, m), 3.13-3.31(2H, m),              4.18-4.40(1H, m), 6.81(1H, d, J=7.5Hz),              6.95-7.10(2H, m)     194      1.65-1.86(2H, m), 1.98(2H, brs),              2.40-2.90(8H, m), 3.15-3.38(2H, m),              4.14-4.48(1H, m), 6.70(1H, dt, J=8.2, 2.3Hz),              6.94(1H, dd, J=11.0, 2.3Hz),              7.09(1H, t, J=8.1Hz)     195      1.62-1.95(3H, m), 2.35(3H, s),              2.38-2.90(8H, m), 3.10-3.48(3H, m),              6.88-7.20(3H, m)     196      1.64-1.83(2H, m), 2.19(3H, s),              2.40-2.86(8H, m), 4.42-4.62(1H, m),              7.08(2H, s), 7.67(1H, s), 7.81(1H, brs)     197      1.27(3H, t, J=7.0Hz), 1.62-1.83(2H, m),              1.91(1H, brs), 2.30-3.32(9H, m),              4.23-4.45(1H, m), 6.96-7.30(4H, m)     198      1.67-1. 86(2H, m), 2.21(1H, brs),              2.43-2.83(8H, m), 2.95(6H, s),              3.15-3.32(2H, m), 4.16-4.40(1H, m),              6.41(1H, dd, J=8.3, 2.3Hz),              6.57(1H, d, J=2.3Hz), 7.01(1H, d, J=8.3Hz)     199      1.56-1.95(2H, m), 2.43-3.23(8H, m),              3.56-3.83(1H, m), 3.67(3H, d, J=9.3Hz),              4.23-4.67(1H, m), 4.86-5.05(1H, m),              6.26-6.42(2H, m), 6.96-7.35(5H, m),              8.57-8.73(1H, m)     200      1.60-1.74(1H, m), 1.80-1.93(1H, m),              2.31(3H, s), 2.47-3.38(8H, m),              3.58-3.75(1H, m), 3.91(3H, d, J=8.9Hz),              4.27-4.69(1H, m), 4.88-5.03(1H, m),              6.67-6.91(2H, m), 6.96-7.30(5H, m)     201      1.52-2.10(6H, m), 2.45-3.10(11H, m),              3.72-5.10(5H, m), 6.90(2H, d, J=8.7Hz),              6.97-7.32(4H, m), 7.43(2H, d, J=8.7Hz)     202      1.26(3H, t, J=7.5Hz), 1.62-1.98(2H, m),              2.35-3.28(10H, m), 3.57-3.98(7H, m),              4.41(1H, brs), 4.85-5.05(1H, m),              6.40-6.60(2H, m), 6.82-7.00(2H, m),              7.08(1H, d, J=7.5Hz), 7.16-7.35(1H, m)     203      1.58-2.00(2H, m), 2.42-3.25(8H, m),              3.60-4.02(10H, m), 4.20-4.70(1H, m),              4.86-5.05(1H, m), 6.42-6.80(4H, m),              7.07(1H, d, J=8.2Hz), 7.13-7.38(1H, m)     204      1.58-2.02(2H, m), 2.50(3H, s),              2.40-3.28(8H, m), 3.57-4.00(4H, m),              4.15-4.78(1H, m), 4.87-5.08(1H, m),              6.65-7.38(6H, m)     205      1.67-1.93(2H, m), 2.33(2H, quint, J=6.1Hz),              2.48-3.15(8H, m), 3.61(2H, t, J=6.4Hz),              3.78-5.28(3H, m), 4.14(2H, t, J=5.8Hz),              6.92(2H, d, J=8.7Hz), 6.98-7.32(4H, m),              7.44(2H, d, J=8.7Hz)     206      1.72-2.13(4H, m), 2.45(2H, t, J=7.0Hz),              2.47-3.35(10H, m), 3.90-4.35(4H, m),              6.55(2H, d, J=8.6Hz), 6.93-7.30(6H, m),              7.33(2H, d, J=8.6Hz), 8.95(1H, brs)     207      1.44-1.97(8H, m), 2.48-3.30(10H, m),              2.96(3H, s), 3.83-5.02(4H, m),              3.98(2H, t, J=6.1Hz), 6.89(2H, d, J=8.7Hz),              6.98-7.35(4H, m), 7.42(2H, d, J=8.7Hz)     208      1.46-2.02(8H, m), 1.97(3H, s),              2.48-3.37(10H, m), 3.80-5.09(3H, m),              3.97(2H, t, J=6.2Hz), 5.87(1H, brs),              6.89(2H, d, J=8.8Hz), 6.95-7.39(4H, m),              7.42(2H, d, J=8.8Hz)     209      1.52-2.03(6H, m), 1.97(3H, s),              2.47-3.40(10H, m), 3.81-4.96(3H, m),              3.99(2H, t, J=6.1Hz), 5.86(1H, brs),              6.88(2H, d, J=8.7Hz), 6.94-7.38(4H, m),              7.42(2H, d, J=8.7Hz)     ______________________________________

Example 384

Acetic acid (30 ml) and 1-(1-benzyl-3-methyl-4-piperidinyl)carbostyril (2.1 g) are added to 10% palladium-carbon (0.5 g) and the mixture is subjected to catalytic reduction at 80° C. under atmospheric pressure. After the catalytic reduction, 10% palladium-carbon is filtered off and the filtrate is concentrated under reduced pressure. Water is added to the residue and the mixture is basified with aqueous sodium hydroxide solution and then extracted with dichloromethane. After washed with water, the extract is dried with magnesium sulfate and the solvent is distilled off under reduced pressure to give 1-(3-methyl-4-piperidinyl)-3,4-dihydrocarbostyril (1.01 g).

NMR (CDCl₃) δ ppm: 1.22 (3H, d, J=7.1 Hz), 1.5-1.7 (1H, m), 2.3-2.5 (1H, m), 2.5-3.3 (9H, m), 4.1-4.3 (1H, m), 6.9-7.1 (1H, m), 7.1-7.3 (3H, m)

The compounds of the above Examples 1-9, 11-164, 169-350, 352-383C are obtained in the same manners as in Example 384.

Example 385

Conc. sulfuric acid (8 ml) is added to N-(β-ethoxyacryloyl)-N-(1-benzoyl-4-piperidinyl)aniline (0.8 g) and the mixture is reacted at 60° C. for 30 minutes. The reaction mixture is poured into ice-water and then extracted with dichloromethane. The solvent is concentrated and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1) to give 1-(1-benzoyl-4-piperidinyl)carbostyril (0.53 g).

NMR (CDCl₃) δ ppm: 1.60-2.02 (2H, m), 2.62-3.41 (4H, m), 3.73-4.26 (1H, m), 4.50-5.72 (2H, m), 6.64 (1H, d, J=9.4 Hz), 7.15-7.70 (10H, m)

The compounds of the above Examples 10 and 166-168 are obtained in the same manners as in Example 385.

Example 386

Ethanol (10 ml) and 10% aqueous sodium hydroxide solution (12 ml) are added to 1-(1-benzoyl-4-piperidinyl)carbostyril (1.0 g) and the mixture is refluxed with heating for 7 hours. After concentration, water is added thereto and the mixture is extracted with dichloromethane. The dichloromethane layer is collected by filtration and water is added thereto. The mixture is acidified with diluted hydrochloric acid. The aqueous layer is basified with diluted aqueous sodium hydroxide solution, extracted with dichloromethane and then concentrated to give 1-(4-piperidinyl)carbostyril (0.58 g).

NMR (CDCl₃) δ ppm: 1.62-2.03 (3H, m), 2.55-3.03 (4H, m), 3.14-3.50 (2H, m), 4.68-5.85 (1H, br), 6.65 (1H, d, J=9.4 Hz), 7.19 (1H, t, J=7.4 Hz), 7.35-8.00 (4H, m)

Using the suitable starting materials, the compounds of the above Examples 156, 158, 171, 186, 351-361 and the following Examples 580, 581 and 577A are obtained in the same manners as in Example 386.

Example 387

1-(4-Piperidinyl)-3,4-dihydrocarbostyril (0.2 g) is added to conc. sulfuric acid (5 ml) and thereto is added fuming nitric acid (0.1 ml) under ice cooling. The mixture is stirred at room temperature for 30 minutes, and then the reaction mixture is poured into ice-water. The mixture is basified and extracted with dichloromethane. The solvent is concentrated to give 6-nitro-1-(4-piperidinyl)-3,4-dihydrocarbostyril (0.2 g).

NMR (CDCl₃) δ ppm: 1.65-2.10 (3H, m), 2.44-3.45 (10H, m), 4.26-4.55 (1H, m), 7.34 (1H, d, J=8.9 Hz), 8.00-8.22 (2H, m)

Using the suitable starting materials, the compounds of the above Examples 3, 38, 43, 163, 175, 188, 195, 379 and the following Example 510 are obtained in the same manners as in Example 387.

Example 388

A mixture of 10% palladium-carbon (0.4 g) and acetic acid (50 ml) is added to 6-nitro-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (4.0 g) and the mixture is subjected to catalytic reduction at 70° C. for 1 hour. The catalyst is filtered off and the filtrate is concentrated. The resulting residue is basified with 10% aqueous sodium hydroxide solution and extracted with dichloromethane. The solvent is concentrated and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=20:1) to give 6-amino-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1.9 g).

NMR (CDCl₃) δ ppm: 1.50-1.93 (2H, m), 2.34-3.20 (8H, m), 3.30-4.15 (9H, m), 4.22-4.75 (1H, m), 4.85-5.03 (1H, m), 6.42-6.63 (4H, m), 6.82-7.33 (2H, m)

Using the suitable starting materials, the compounds of the above Examples 48, 80, 182, 176, 192, 380 and the following Examples 485, 511 are obtained in the same manners as in Example 388 and in following Example 401.

Example 389

Dichloromethane (10 ml) and triethylamine (0.15 ml) are added to 6-amino-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.3 g). Acetic anhydride (0.2 ml) is added thereto and the mixture is stirred at room temperature for 1 hour. Water is added to the reaction mixture and extracted with dichloromethane. After concentration, the residue is purified by silica gel column chromatography (solvent; chloroform:methanol=20:1) and further recrystallized from ethanol to give 6-acetylamino-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.25 g) as white powder, m.p. 271°-272° C.

The compounds of the above Examples 160, 267, 359 and the following Examples 484 and 486 are obtained in the same manners as in Example 389.

Example 390

7-Fluoro-1-(4-piperidinyl)-3,4-dihydrocarobstyril (2.37 g), 2-methoxy-4-ethoxybenzoic acid (2.43 g) and bis(2-oxo-oxazolydinyl)phosphinyl chloride (3.65 g) are dissolved in dichloromethane (50 ml) and thereto is added dropwise triethylamine (4 ml). The mixture is stirred at room temperature overnight and poured into water. The mixture is extracted with dichloromethane, dried with sodium carbonate and then purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=1:1). The resultant is recrystallized from ethanol/water to give 7-fluoro-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (2.5 g) as white powder, m.p. 159°-161° C.

Example 391

1-(4-Piperidinyl)-3,4-dihydrocarbostyril (500 mg) and triethylamine (0.6 ml) are dissolved in dichloromethane (10 ml) and thereto is added dropwise ethyl chlorocarbonate (0.31 ml) gradually. The mixture is stirred at room temperature for 2 hours and poured into water. The mixture is extracted with chloroform, dried with sodium carbonate and purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=3:1). The resultant is re-crystallized from ethanol/n-hexane to give 1-(1-ethoxycarbonyl-4-piperidinyl)-3,4-dihydrocarbostyril (0.1 g) as white powder, m.p. 82°-83° C.

Example 392

1-(4-Piperidinyl)-3,4-dihydrocarbostyril (500 mg), triethylamine (1.2 ml) and pyrrole-2-carboxylic acid (314 mg) are dissolved in dichloromethane (10 ml) and thereto is added dropwise diethyl cyanophosphate (0.82 ml) under ice cooling. The mixture is stirred with ice cooling for 1 hour and then stirred at room temperature for 2 hours. The mixture is poured into water, extracted with chlorform, dried with sodium carbonate and purified by silica gel column chromatography (solvent; dichloromethane:methanol=20:1). The resultant is recrystallized from n-hexane/diethyl ether to give 1-[1-(2-pyrrolylcarbonyl)-4-piperidinyl]-3,4-dihyrocarbostyril (0.2 g), as white powder, m.p. 161°-162° C. (decomposed).

Example 393

1-(4-Piperidinyl)-3,4-dihydrocarbostyril (0.8 g) is dissolved in dichloromethane (20 ml) and thereto is added phenylisocyanate (0.57 ml) and the mixture is stirred at room temperature for 4 hours. The solvent is concentrated and the residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=5:1) and recrystallized from n-hexane/ethanol to give 1-(1-anilinocarbonyl-4-piperidinyl)-3,4-dihydrocarbostyril (0.8 g), as white powder, m.p. 194°-196° C.

The compounds of the above Examples 1-155, 157, 159-167, 169-170, 173-182, 187-232, 234-235, 241-243, 246-290, 294-346, 348-350, 362-383C and the following Examples 436, 438, 440, 442, 443-460, 465-475, 482-579 and 582-587 are obtained in the same manners as in Examples 390-393.

Example 394

1-[1-(4-α-t-Butoxycarbonylaminophenylacetyl)-4-piperidinyl]-3,4-dihydrocarbostyril (400 mg) is dissolved in formic acid (5 ml) and the mixture is stirred at room temperature overnight. The solvent is distilled off under reduced pressure and the resulting oily product is purified by silica gel column chromatography (solvent; dichloromethane:methanol=8:1). The resultant is recrystallized from diethyl ether to give 1-[1-(4-α-aminophenylacetyl)-4-piperidinyl)-3,4-dihydrocarbostyril (0.22 g), as white powder, m.p. 116°-120° C.

Example 395

A mixture (5 ml) of hydrobromic acid and acetic acid (35% solution) is added to 1-{1-[4-(N-t-butoxycarbonyl-N-methylamino)benzoyl]-4-piperidinyl}-3,4-dihyrocarbostyril (1.8 g) and the mixture is stirred at room temperature overnight. The reaction mixture is poured into water and the pH value thereof is adjusted to pH 12-14 by adding potassium carbonate. The mixture is extracted with chloroform, dried with sodium carbonate and then purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=1:1). The resultant is recrystallized from n-hexane/ethanol to give 1-{1-[4-(N-methylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.2 g), as white powder, m.p. 184°-186° C.

Example 396

1-[1-(1-Benzyloxycarbonyl-2-pyrrolidinylcarbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.87 g) is dissolved in ethanol (20 ml) and thereto is added 5% palladium-carbon (0.1 g). The mixture is stirred at room temperature under 1 atm. under hydrogen atmosphere. After the completion of the reaction, the catalyst is filtered off and the filtrate is concentrated. The resultant is purified by silica gel column chromatography (solvent; dichloromethane:methanol=8:1) to give 1-[1-(2-pyrrolidinylcarbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril (205 mg).

NMR (CDCl₃) δ ppm: 1.72-2.29 (6H, m), 2.39-2.92 (7H, m), 3.10-3.32 (1H, m), 3.35-3.65 (2H, m), 3.82-4.25 (2H, m), 4.52-4.90 (2H, m), 6.30-7.35 (5H, m)

Example 397

1-[1-(4-Benzyloxybenzoyl)-4-piperidinyl]-3,4-dihyrocarbostyril (4.76 g) is dissolved in methanol (100 ml) and thereto is added 5% palladium-carbon (1 g). The mixture is stirred at room temperature under 1 atm. under hydrogen atmosphere. After the completion of the reaction, the catalyst is filetered off and the filtrate is concentrated. The resultant is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=1:1) and further recrystallized from n-hexane/ethanol to give 1-[1-(4-hydroxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (2.5 g) as white powder, m.p. 182°-183° C.

Example 398

60% Sodium hydride (0.34 g) is washed with n-hexane and thereto is added dimethylformamide (20 ml). Thereto are added 1-[1-(4-hydroxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1 g), 2-chloroethyldimethylamine hydrochloride (0.66 g) and sodium iodide (1.7 g) and the mixture is stirred at 50°-60° C. under argon atmosphere for 2 hours. Then, the mixture is further stirred at room temperature overnight. The reaction mixture is poured into water and extracted with ethyl acetate/toluene, dried with sodium carbonate. The resultant is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=1:1) to give 1-{1-[1-(2-dimethylaminoethoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.362 g).

NMR (DMSO-d₆) δ ppm: 1.72-1.94 (2H, m), 2.48-3.26 (10H, m), 2.66 (6H, s), 3.77-5.28 (5H, m), 6.94-7.45 (6H, m)

Example 399

1-[1-(4-Hydroxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (500 mg), prenyl bromide (0.5 ml) and 1,8-diazabicyclo[5.4.0]-undecene-7 (0.65 ml) are dissolved in isopropanol (10 ml) and the mixture is refluxed with heating for 4 hours. The solvent is distilled off under reduced pressure and the residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=2:1) to give 1-{1-[4-(2-isopentenyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.159 g).

NMR (CDCl₃) δ ppm: 1.56-1.79 (2H, m), 1.75 (3H, s), 1.80 (3H, s), 2.47-3.14 (8H, m), 3.93-5.05 (3H, m), 4.53 (2H, d, J=6.8 Hz), 5.40-5.57 (1H, m), 6.83-7.53 (8H, m)

The compounds of the above Examples 10, 19, 23, 26, 30, 31, 33, 38, 44, 45, 47, 50, 54, 55, 56, 61, 66, 72, 74, 76, 84, 89, 91, 94, 95, 98, 99, 102, 106, 108-110, 113-115, 118-119, 121-155, 157, 159-164, 166, 167, 170, 172-180, 189, 194, 209, 212, 222-225, 227, 228, 230-232, 234-235, 241-243, 246-251, 254-256, 260-280, 285, 288-294, 296, 297, 299-328, 332-335, 338, 345, 348, 350, 362-365, 367-373, 377-378, 383A-383C and the following Examples 436, 438, 440, 442, 445, 472, 475, 482-577, 582-587 are obtained in the same manners as in Examples 398 and 399.

Example 400

Trifluoroacetic acid (0.21 ml) is added dropwise with stirring to a mixture of 1-{1-[4-(3-hydroxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.51 g), NaOCN (0.16 g), toluene (5 ml) and chloroform (5 ml) at room temperature. After adding, the mixture is stirred at room temperature overnight. Ethyl acetate is added to the reaction mixture and the mixture is washed with saturated aqueous sodium hydrogen carbonate solution, water and saline solution successively and then dried with sodium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1) to give 1-{1-[4-(3-carbamoyloxypropoxy)benzoyl-4-piperidinyl}-3,4-dihydrocarbostyril (0.15 g).

NMR (CDCl₃) δ ppm: 1.60-2.32 (4H, m), 2.41-3.27 (8H, m), 3.71-5.15 (5H, m), 4.07 (2H, t, J=6.2 Hz), 4.26 (2H, t, J=6.2 Hz), 6.96 (2H, d, J=8.6 Hz), 6.99-7.40 (4H, m), 7.43 (2H, d, J=8.6 Hz)

The compounds of the above Examples 128, 313 and the following Examples 470, 569 are obtained in the same manners as in Example 400.

Example 401

1-[1-(4-Nitrobenzoyl)-4-piperidinyl-3,4-dihydrocarbostyril (4.21 g) is dissolved in ethanol (100 ml) and thereto is added 5% palladium-carbon (1 g) and the mixture is stirred at room temperature under 1 atm. under hydrogen atomsphere. After the reaction, the catalyst is removed by fileration. The filtrate is concentrated and the residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=20:1) and recrystallized from n-hexane/ethanol to give 1-[1-(4-aminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (2.1 g) as white powder, m.p.: 198°-199° C.

Example 402

1-[1-(4-Methoxycarbonylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (6.33 g) and sodium hydroxide (1.94 g) are dissolved in methanol (100 ml) and the mixture is stirred at room temperature overnight. After the solvent is concentrated, water is added to the residue and the mixture is extracted with diethyl ether. The aqueous layer is adjusted to pH 1 by adding conc. hydrochloric acid and extracted with ethyl acetate. The extract is dried with magnesium sulfate, concentrated and recrystallized from n-hexane/ethanol to give 1-[1-(4-carboxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (4.5 g) as white powder, m.p.: 232°-235° C.

Using the suitable starting materials, the compounds of the above Examples 260, 275, 301, 303, 304, 308, 310, 316, 336, 365, 374 and the following Example 482 are obtained in the same manners as in Example 402.

Example 403

1-{1-[4-(N-methylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (200 mg) is dissolved in dichloromethane (5 ml) and thereto is added α-chloroacetyl chloride (55 μl) under ice cooling. Continually thereto is added triethylamine (0.23 ml) and the mixture is stirred at room temperature overnight. After the solvent is concentrated, the residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane/ethanol to give 1-{1-[4-(N-α-chloroacetyl-N-methylamino)benzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.18 g) as white powder, m.p.: 220°-222° C. (decomposed).

Example 404

1-[1-(4-Aminobenzoyl)-1-piperidinyl]-3,4-dihydrocarbostyril (4 g) is dissolved in dichloromethane (100 ml) and thereto is added trifluoroacetic anhydride (2.1 ml). Under ice cooling, thereto is added dropwise triethylamine (4.78 ml) and the mixture is stirred at the same temperature for 2 hours and then at room temperature overnight. The reaction mixture is poured into water and extracted with chloroform and dried with magnesium sulfate. The resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane to give 1-[1-(4-trifluoroacetylamino)-4-piperidinyl]-3,4-dihydrocarbostyril (3.8 g) as light red powder, m.p.: 104°-107° C.

Example 405

A mixture of 1-[1-(2-aminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.96 g), acetic anhydride (10 ml) and conc. sulfuric acid (0.1 ml) is stirred at room temperature for 2 hours. The reaction mixture is basified with 1N aqueous sodium hydroxide solution and extracted with ethyl acetate. The extract is washed successively with saturated aqueous sodium hydrogen carbonate solution, 1N hydrochloric acid and saturated saline solution and dried with sodium sulfate. After the solvent is distilled off, the residue is recrystallized from ethyl acetate/diethyl ether to give 1-[1-(2-acetylaminobenzoly)-4-piperidinyl]-3,4-dihydrocarbostyril (0.55 g) as colorless needles, m.p.: 141°-143° C.

Using the suitable starting materials, the compounds of the above Examples 32, 57-59, 67, 78, 87, 88, 116, 129, 130, 137, 140-141, 145, 149-152, 155, 174, 187, 200, 246, 254, 255, 288, 291, 292, 382, 383, 383B, 383C and the following Examples 451, 452, 463, 467, 468, 469, 488, 500-503, 506-508, 510, 511, 513-515, 519-521, 523, 536, 537, 587 are obtained in the same manners as in Examples 403-405.

Example 406

1-[1-(3-Ethoxycarbonylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.5 g), aqueous ammonia (10 ml) and ammonium chloride (the effective amount as a catalyst) are dissolved in ethanol (10 ml) and the mixture is stirred at 110°-130° C. for 10 hours in an autoclave. Ethanol is distilled off under reduced pressure and the residue is extracted with methylene chloride. The organic layer is washed with water and saturated saline solution, dried with sodium sulfate and concentrated. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: methylene chloride:methanol=10:1) to give 1-[1-(3-carbamoylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.15 g).

NMR (CDCl₃) δ ppm: 1.59-2.11 (2H, m), 2.48-3.33 (8H, m), 3.70-5.15 (3H, m), 5.58-6.60 (2H, m), 6.97-8.05 (8H, m)

Using the suitable starting materials, the compounds of the above Examples 276, 294, 300, 305, 307, 309, 313, 317-319, 321, 326, 329 and 344 are obtained in the same manners as in Example 406.

Example 407

A mixture of 1-{1-[4-3-methylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.5 g), propyl bromide (0.13 ml), sodium hydrogen carbonate (0.15 g) and acetonitrile (10 ml) is stirred at room temperature for 8 hours. Further thereto are added propyl bromide (0.13 ml) and sodium hydrogen carbonate (0.15 g) and the mixture is stirred with heating at 60° C. for 8 hours. The solvent is distilled off and the resulting residue is extracted with ethyl acetate. The extract is washed successively with saturated sodium hydrogen carbonate, water and saline solution and dried with sodium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=20:1) to give 1-[1-{4-[3-(N-methyl-N-propylamino)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (0.15 g).

NMR (CDCl₃) δ ppm: 0.91 (3H, t, J=5.8 Hz), 1.42-3.31 (21H, m), 2.33 (3H, s), 3.88-5.15 (3H, m), 4.05 (2H, t, J=5 Hz), 6.91 (2H, d, J=7 Hz), 6.95-7.38 (4H, m), 7.42 (2H, d, J=7 Hz)

Example 408

A mixture of 1-{1-[4-(3-aminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.4 g), benzaldehyde (0.42 ml) and methanol (15 ml) is stirred at room temperature for 3 hours and cooled with ice. Thereto is added sodium boron hydride (0.21 g) and the mixture is stirred under ice cooling for 2 hours and then allowed to stand at room temperature overnight. The solvent is distilled off and water is added to the resulting residue and the mixture is extracted with ethyl acetate. The extract is washed successively with saturated sodium hydrogen carbonate, water and saline solution, dried with sodium sulfate and then the solvent is distilled off. The resulting residue is purified by silica gel column chromatography (solvent: methanol:dichloromethane=1:100) to give 1-{1-[4-benzylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.02 g).

NMR (CDCl₃) δ ppm: 1.60-2.15 (5H, m), 2.47-3.18 (10H, m), 3.82 (2H, s), 3.95-5.11 (3H, m), 4.08 (3H, t, J=6.2 Hz), 6.89 (2H, d, J=8.5 Hz), 6.95-7.50 (9H, m), 7.42 (2H, d, J=8.5 Hz)

Example 409

1-[1-(2-Methoxy-4-methylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (500 mg) is dissolved in methanol (10 ml) and thereto is added formaldehyde (0.54 ml) and then thereto is added NaBH₃ CN (86.4 mg) under ice cooling. The mixture is stirred under ice cooling for 2 hours and further stirred at room temperature. The reaction mixture is concentrated and to the residue is added saturated aqueous sodium hydrogen carbonate solution. The mixture is extracted with chloroform and dried with sodium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane/ethanol to give 1-[1-(2-methoxy-4-dimethylaminobenzoyl)-4-piperazinyl]-3,4-dihydrocarbostyril (0.263 g) as white powder, m.p.: 93°-96° C.

Using the suitable starting materials, the compounds of the above Examples 27, 40, 55, 57, 59, 62, 63, 65, 67, 68, 76, 79, 81, 82, 88, 89, 92, 114, 115, 118, 119, 123, 124, 126, 127, 131, 133, 138, 139, 143, 144, 149, 150-152, 169, 184, 185, 187, 190, 198, 199, 214, 231, 236-238, 242-246, 248, 251, 254, 255, 261-263, 265, 268, 270, 283, 285, 287, 291-293, 305, 306, 309, 311, 321, 322, 326, 327, 332, 334, 335, 344, 346, 349, 361, 366, 367, 374, 381, 383A and the following Examples 448, 449, 454, 455, 456, 458, 459, 464, 466, 474A, 489-496, 498, 499, 504, 505, 509, 516-518, 522, 532, 539-546, 550-552, 554-556, 559, 562-565 and 567 are obtained in the same manners as in Examples 407-409.

Example 410

A mixture of 1-[1-{4-[3-(N-benzyl-N-methylamino)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (5.3 g), 5% palladium-carbon (0.8 g), ammonium formate (2.6 g) and ethanol (300 ml) is refluxed with heating for 2 hours. The catalyst is filtered off and ethanol is distilled off under reduced pressure. To the residue is added chloroform and the mixture is washed successively with saturated sodium hydrogen carbonate, water and saline solution. Further the mixture is dried with sodium sulfate and the solvent is distilled off. The resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=20:1→5:1) to give 1-[1-{4-[3-(N-methylamino)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (4.37 g).

This product is dissolved in acetone and converted into hydrochloride salt thereof in hydrochloric acid/ethanol. The precipitated crystal is collected by filtration and recrystallized from ethanol/acetone/diethyl ether to give 1-[1-{4-[3-(N-methylamino)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril hydrochloride as colorless needles, m.p.: 89°-93° C.

Example 411

1-[1-{4-[3-(Phthalimido-1-yl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (9.5 g), hydrazine hydrate (1.03 ml) and ethanol (100 ml) are refluxed with heating for 2.5 hours. After cooling, the mixture is adjusted to pH 1 by adding conc. hydrochloric acid and the precipitated materials are filtered off. Most of ethanol is distilled off from the filtrate and water is added to the residue. The insoluble materials are filtered off and the mother liquid is basified with 5N sodium hydroxide, extracted with ethyl acetate. The organic layer is washed with saturated saline solution and dried with sodium sulfate, concentrated. The residue is purified by silica gel column chromatography (solvent: methylene chloride:methanol=15:1) to give 1-{1-[4-(3-aminopropoxy)benzoyl]-4-piperidinyl]-3,4-dihydrocarbostyril (5.18 g).

NMR (CDCl₃) δ ppm: 1.64-2.10 (4H, m), 2.97-3.18 (8H, m), 2.92 (2H, t, J=6.8 Hz), 4.08 (2H, t, J=6.1 Hz), 4.10-5.15 (3H, m), 6.82-7.58 (8H, m)

Using the suitable starting materials, the compounds of the above Examples 136, 148, 154 and the following. Examples 473 and 586 are obtained in the same manners as in Example 411.

Example 412

1-{1-[4-(3-Aminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.5 g), methylisocyanate (0.15 ml) and acetone (10 ml) are heated at 100° C. for 18 hours in an autoclave. Acetone is distilled off and the residue is purified by silica gel column chromatography (solvent: methylene chloride:methanol=100-50:1) to give 1-{1-[4-(3-(3-methylureido)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.19 g).

NMR (CDCl₃) δ ppm: 1.55-2.20 (4H, m), 2.49-3.50 (10H, m), 2.96 (3H, m), 3.90-5.13 (4H, m), 4.09 (2H, t, J=5.7 Hz), 6.90 (2H, d, J=8.7 Hz), 6.95-7.38 (4H, m), 7.43 (2H, d, J=8.7 Hz)

Example 413

A mixture of formic acid (0.19 ml) and acetic anhydride (0.4 ml) is stirred with heating at 50°-60° C. for 1.5 hour. Thereto is added 1-{1-[4-(4-aminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.6 g) at room temperature and the mixture is stirred at room temperature for 13 hours. The reaction mixture is poured into ice-water and extracted with ethyl acetate. The extract is washed with aqueous sodium hydrogen carbonate, water and saline solution and dried with sodium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=50:1→25:1) to give 1-{1-[4-(4-formylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.49 g).

NMR (CDCl₃) δ ppm: 1.55-2.00 (6H, m), 2.45-3.48 (10H, m), 3.76-5.10 (3H, m), 3.99 (2H, t, J=5.7 Hz), 5.74-6.25 (1H, m), 6.78-7.53 (8H, m), 8.15 (1H, s)

Using the suitable starting materials, the compounds of the above Example 130 and the following Examples 488 and 508 are obtained in the same manners as in Example 413.

Example 414

1-[1-(4-Formylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (500 mg) is dissolved in methanol (10 ml) and thereto is added sodium boron hydride (63 mg) under ice cooling and the mixture is stirred for 2 hours. The solvent is concentrated and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=2:1) and recrystallized from n-hexane/ethanol to give 1-[1-(4-hydroxymethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (390 mg) as white powder, m.p.: 138°-139° C.

Using the suitable starting materials, the compounds of the above Examples 83, 85 and the following Examples 444 and 456 are obtained in the same manners as in Example 414.

Example 415

60% Sodium hydride (147 mg) is washed with n-hexane and thereto is added dimethylformamide (10 ml) under argon atmosphere. To the mixture is added 1-[1-(4-trifluoroacetylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1 g) under ice cooling, and the mixture is stirred for a while and then thereto is added dropwise allyl bromide (0.32 ml). The mixture is stirred under ice cooling for 1 hour and then at room temperature overnight to give 1-{1-[4-(N-trifluoroacetyl-N-allylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. To this product are added water (20 ml) and sodium hydroxide (0.1 g) and the mixture is stirred for 4 hours. The reaction mixture is poured into water and extracted with ethyl acetate/toluene (1:1), dried with sodium carbonate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-[1-(4-allylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.5 g).

NMR (CDCl₃) δ ppm: 1.72-1.92 (2H, m), 2.52-3.12 (8H, m), 3.72-3.88 (2H, m), 4.07 (1H, brs), 4.15-4.76 (3H, m), 5.14-5.35 (2H, m), 5.83-6.04 (1H, m), 6.56-6.62 (2H, m), 6.98-7.37 (6H, m)

Example 416

1-[1-(2-Methoxy-4-methylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (500 mg) is dissolved in methanol (10 ml) and thereto is added a solution of NaIO₄ (391 mg) in water (4 ml) and the mixture is stirred at room temperature overnight. The solvent is distilled off under reduced pressure, and water is added to the resulting residue. The mixture is extracted with chloroform, dried with magnesium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=2:1) and recrystallized from n-hexane/ethanol to give 1-[1-(2-methoxy-4-methylsulfinylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.31 g) as white powder, m.p.: 95°-98° C.

Using the suitable starting meterials, the compounds of the above Examples 51, 368 and the following Example 570 are obtained in the same manners as in Example 416.

Example 417

1-[1-(2-Methoxy-4-acetyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.4 g) and sodium hydroxide (0.5 g) are dissolved in methanol (20 ml) and the mixture is stirred at room temperature for 1 hour. The solvent is concentrated and water is added to the residue, then the mixture is extracted with chloroform, dried with magnesium sulfate. The solvent is ditilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-[1-(2-methoxy-4-hydroxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.3 g).

NMR (CDCl₃) δ ppm: 1.56-1.95 (2H, m), 2.43-3.23 (8H, m), 3.56-3.83 (1H, m), 3.67 (3H, d, J=9.3 Hz), 4.23-4.67 (1H, m), 4.86-5.05 (1H, m), 6.26-6.42 (2H, m), 6.96-7.35 (5H, m), 8.57-8.73 (1H, m)

Example 418

1-{1-[4-(2-Cyclohexenyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (200 mg) is dissolved in ethanol (5 ml) and thereto is added 10% palladium-carbon (50 mg). The mixture is stirred at room temperature under atmospheric pressure under hydrogen atmosphere. After the completion of the reaction, the catalyst is removed by filtration. The resulting filtrate is concentrated and purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-[1-(4-cyclohexyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (174 mg).

NMR (CDCl₃) δ ppm: 1.20-2.10 (12H, m), 2.44-3.13 (8H, m), 3.78-5.08 (4H, m), 6.90 (2H, d, J=8.7 Hz), 6.97-7.32 (4H, m), 7.40 (2H, d, J=8.7 Hz)

Example 419

1-[1-(4-Formylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1 g), hydroxylamine hydrochloride (580 mg) and sodium acetate (1.6 g) are dissolved in ethanol (20 ml) and water (10 ml) and the mixture is stirred at room temperature overnight. The solvent is concentrated and water is added to the residue. The mixture is extracted with chloroform, dried with sodium carbonate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:2) and recrystallized from n-hexane/ethanol to give 1-[1-(4-hydroxyiminomethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1 g) as white powder, m.p.: 222°-224° C.

Example 420

1-[1-(4-Aminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (500 mg) and 2,5-dimethoxytetrahydrofuran (0.19 ml) are refluxed-with heating for 2 hours in acetic acid. The solvent is concentrated and the residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane to give 1-{1-[4-(1-pyrrolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (228 mg) as light gray powder, m.p.: 153°-156° C.

Example 421

1-[1-(4-Glycidoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (200 mg) is dissolved in methanol (4 ml) and thereto is added diethylamine (0.26 ml) and the mixture is stirred at room temperature overnight, and then refluxed with heating for 3 hours. The solvent is concentrated and the residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1→dichloromethane:methanol=10:1) to give 1-{1-[4-(3-diethylamino-2-hydroxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.18 g).

This product is stirred with the equivalent amount of citric acid in diethyl ether to give citrate salt thereof as white powder, m.p.: 72°-76° C. (recrystallized from diethyl ether).

Using the suitable starting materials, the compounds of the above Examples 118, 119, 335 and the following Examples 448, 474A, 489, 532-535, 537, 538, 541-558, 562-567 are obtained in the same manners as in Example 421.

Example 422

1-[1-(4-Cyanobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1 g) is dissolved in chloroform (10 ml) and thereto is added ethanol (0.18 ml). Under ice cooling, hydrochloric acid gas is passed through the mixture to saturate and further the mixture is stirred at 5°-7° C. for 4 days. After the reaction, the solvent is concentrated to give 1-{1-[4-(1-ethoxy-1-iminomethyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1 g). This product is used for the subsequent reaction.

1-{1-[4-(1-Ethoxy-1-iminomethyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1 g) is dissolved in methanol (10 ml) and thereto is added aqueous ammonia (10 ml) and the mixture is stirred at room temperature overnight. The solvent is concentrated and water is added to the residue. The mixture is extracted with chloroform, dried with sodium carbonate, concentrated and then purified by silica gel column chromatography (solvent: chloroform:methanol=10:1) and recrystallized from ethanol/n-hexane to give 1-[1-(4-carbamoyl-4-piperidinyl]-3,4-dihydrocarbostyril (0.2 g) as white powder, m.p.: 101°-104° C.

Further, the aqueous layer is concentrated and the resulting residue is recrystallized from water to give 1-[1-(4-amidinobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.4 g) as white powder, m.p.: 92°-97° C.

NMR (CDCl₃) δ ppm: 1.55-1.92 (2H, m), 2.32-3.05 (7H, m), 3.12-3.62 (2H, m), 4.22-4.72 (2H, m), 6.92-7.38 (4H, m), 7.63 (2H, d, J=8.2 Hz), 7.92 (2H, d, J=8.2 Hz), 9.48 (3H, brs)

Using the suitable starting materials, the compound of the above Example 113 is obtained in the same manners as in Example 422.

Example 423

1-{1-[4-(4-Pentenyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2 g) is dissolved in dichloromethane (50 ml) and thereto is added gradually m-chloroperbenzoic acid (1.6 g) at room temperature. The mixture is stirred under the same conditions overnight and the reaction mixture is poured into aqueous sodium hydrogen carbonate solution and the mixture is extracted with chloroform and dried with magnesium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-{1-[4-(3-oxiranylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.5 g).

NMR (CDCl₃) δ ppm: 1.52-2.10 (6H, m), 2.45-3.10 (11H, m), 3.72-5.10 (5H, m), 6.90 (2H, d, J=8.7 Hz), 6.97-7.32 (4H, m), 7.43 (2H, d, J=8.7 Hz)

Using the suitable starting materials, the compounds of the above Example 333 and the following Example 572 are obtained in the same manners as in Example 423.

Example 424

1-[1-(4-Formylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (4.77 g) is dissolved in methanol (100 ml) and thereto is added carbomethoxymethylenetriphenylphosphorane (5.3 g) and the mixture is stirred at room temperature for 1 hour. The solvent is concentrated and the residue is purified roughly by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give a mixture (8 g) of 1-{1-[4-(2-methoxycarbonylvinyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril and triphenylphosphineoxide.

This mixture is dissolved in ethanol (100 ml) and thereto is added 10% palladium-carbon (1 g). The mixture is stirred at room temperature under 1 atm. under hydrogen atmosphere. After the reaction, the catalyst is removed by filtration and the resulting filtrate is concentrated. The resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane to give 1-{1-[4-(2-methoxycarbonylethyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (3 g) as white powder, m.p.: 85°-86° C.

Using the suitable starting materials, the compounds of the above Examples 220, 336 and 339 are obtained in the same manners as in Example 424.

Example 425

To a mixture of propyltriphenylphosphonium bromide (2.34 g), potassium-t-butoxide (62 mg) and sodium amide powder (0.3 g) is added tetrahydrofuran (110 ml) under argon atmosphere and the mixture is stirred at room temperature for 3 hours. To the resulting yellowish red solution is added 1-[1-(4-formylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (2 g) gradually under ice cooling and the mixture is stirred under the same conditions for 3 hours. The reaction mixture is poured into water and extracted with ethyl acetate/toluene and then dried over sodium carbonate. The resultant is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-{1-[4-(1-butenyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2 g).

NMR (CDCl₃) δ ppm: 1.05-1.33 (3H, m), 1.66-2.02 (2H, m), 2.30-3.26 (10H, m), 3.85-5.13 (3H, m), 5.69-5.83, 6.35-6.75 (2H, m), 7.02-7.54 (8H, m)

Example 426

Ethanethiol (0.125 ml) is dissolved in methanol (10 ml) and thereto is added sodium methoxide (0.11 g). The mixture is stirred at room temperature for 30 minutes. Thereto is added a solution of 1-{1-[4-(3-bromopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.59 g) in methanol (2 ml) and the mixture is stirred at room temperature overnight. The solvent is concentrated and water is added to the residue, extracted with chloroform, dried with sodium carbonate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) to give 1-{1-[4-(3-ethylthiopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.2 g).

NMR (CDCl₃) δ ppm: 1.27 (3H, t, J=7.4 Hz), 1.68-1.92 (2H, m), 1.98-2.18 (2H, m), 2.45-3.14 (10H, m), 3.70-5.15 (3H, m), 4.10 (2H, t, J=6.1 Hz), 6.91 (2H, d, J=8.6 Hz), 6.99-7.32 (4H, m), 7.43 (2H, d, J=8.6 Hz)

Using the suitable starting materials, the compounds of the above Example 40, 55, 56, 66, 114, 115, 129, 132, 133, 135, 136, 137-141, 143, 145, 146, 147, 148, 153-155, 234, 235, 241-243, 246, 249, 250, 251, 255, 261, 262, 268-270, 276, 294, 300, 305-307, 309, 311, 317-319, 321, 322, 325-327, 332, 367, 383A-383C and the following Examples 445, 449-459, 466-469, 471-473, 488-496, 498-531, 539-540, 559-560, 569, 585-587 are obtained in the same manners as in Example 426.

Example 427

1-[1-(4-Vinylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.6 g) is dissolved in ethanol (10 ml) and thereto is added 10% palladium-carbon (0.1 g) and the mixture is stirred under hydrogen atmosphere. After the reaction, the catalyst is removed by filtration and the filtrate is concentrated. The resultant is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane/ethanol to give 1-[1-(4-ethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.5 g) as white powder, m.p.: 133°-134° C.

Using the suitable starting materials, the compounds of the above Examples 69, 220 and 339 are obtained in the same manners as in Example 427.

Example 428

1-[1-(4-Allyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (1.15 g) is dissolved in N,N-dimethylaniline (5 ml) and the mixture is heated at 180°-190° C. for 8 hours. After cooling, the reaction mixture is adjusted to around pH 4 by adding hydrochloric acid thereto. The mixture is extracted with dichloromethane and dried with magnesium sulfate. The solvent is distilled off and the residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=3:1→1:3) and further purified by silica gel column chromatography (solvent: dichloromethane:methanol=100:1) and recrystallized from dichloromethane/n-hexane to give 1-[1-(4-hydroxy-3-allylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (0.22 g) as white powder, m.p.: 87°-90° C.

Using the suitable starting materials, the compound of the above Example 282 is obtained in the same manners as in Example 428.

Example 429

To a solution of 1-(4-aminophenyl)-3,4-dihydrocarbostyril (0.45 g) in dichloromethane (15 ml) is added triethylamine (0.29 g). Thereto is added 2,4-dimethoxybenzoyl chloride (0.42 g) with stirring under ice cooling. The mixture is refluxed with heating for 0.5 hour. After cooling, water is added thereto and the mixture is extracted with dichloromethane, washed with water and then dried with magnesium sulfate. The solvent is distilled off under reduced pressure and the residue is purified by silica gel column chromatography and recrystallized from ethanol/diethyl ether/n-hexane to give 1-[4-(2,4-dimethoxybenzoylamino)phenyl]-3,4-dihydrocarbostyril (0.44 g) as white powder, m.p.: 226°-227° C.

Using the suitable starting materials, the compound of the above Example 292 is obtained in the same manners as in Example 429.

Example 430

To a solution of 1-[4-(4-methoxyanilinocarbonyl)phenyl]-3,4-dihydrocarbostyril (0.2 g) in dimethylformamide (15 ml) is added 60% sodium hydride (24 mg) with stirring under ice cooling and the mixture is stirred at room temperature for 0.5 hour. Then, thereto is added a solution of ethyl bromide (64 mg) in dimethylformamide (DMF, 1 ml) and the mixture is refluxed with heating for 1 hour. DMF is distilled off under reduced pressure and water is added to the residue and the mixture is extracted with dichloromethane. The extract is washed with water and dried with magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography to give 1-[4-(N-ethyl-4-methoxyanilinocarbonyl)phenyl]-3,4-dihydrocarbostyril (0.12 g).

NMR (CDCl₃) δ ppm: 2.76 (3H, t, J=8.1 Hz), 3.0 (3H, t, J=8 Hz), 3.48 (3H, s), 3.75 (3H, s), 6.19 (1H, dd, J=3.1 Hz, 6 Hz), 6.78 (2H, d, J=8.3 Hz), 6.9-7.2 (7H, m), 7.43 (2H, d, J=8.4 Hz)

Example 431

To a solution of 1-[4-(2,4-dimethoxybenzoylamino)phenyl]-3,4-dihydrocarbostyril (0.19 g) in dimethylformamide (8 ml) is added with stirring 60% sodium hydride (0.02 g) under ice cooling. The mixture is stirred at room temperature for 0.5 hour and thereto is added a solution of methyl iodide (0.08 g) in dimethylformamide (6 ml). The mixture is stirred at room temperature for 3 hours. The solvent is distilled off under reduced pressure and water is added to the residue. The mixture is extracted with dichloromethane, washed with water and dried with magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography to give 1-{4-[N-(2,4-dimethoxybenzoyl)-N-methylamino]phenyl}-3,4-dihydrocarbostyril (70 mg).

NMR (CDCl₃) δ ppm: 2.78 (3H, t, J=8 Hz), 3.04 (3H, t, J=8 Hz), 3.50 (3H, s), 3.59 (3H, s), 3.76 (3H, s), 6.0-6.1 (1H, m), 6.2 (1H, brs), 6.41 (1H, dd, J=2.3 Hz, 8.4 Hz), 6.9-7.1 (4H, m), 7.1-7.3 (4H, m)

Using the suitable starting materials, the compounds of the above Examples 245, 236, 237, 172, 292 and 347 are obtained in the same manners as in Examples 430 and 431.

Example 432

To a solution of 1-(4-carboxyphenyl)-3,4-dihydrocarbostyril (0.2 g) in chloroform (5 ml) is added thionyl chloride (0.8 ml) and the mixture is refluxed with heating for 1 hour. Then, chloroform and thionyl chloride are distilled off under reduced pressure to give 4-(3,4-dihydrocarbostyril-1-yl)benzoic acid chloride.

To a solution of p-anisidine (0.11 g) in chloroform (5 ml) is added triethylamine (0.15 g) and thereto is added with stirring a solution of 4-(3,4-dihydrocarbostyril-1-yl)benzoic acid chloride obtained above in chloroform (2 ml) under ice cooling. The mixture is stirred at room temperature overnight. Water is added to the reaction mixture and the mixture is extracted with dichloromethane, washed with water and dried with magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is crystallized from diethyl ether and further recrystallized from ethanol/diethyl ether/n-hexane to give 1-[4-(4-methoxyanilinocarbonyl)phenyl]-3,4-dihydrocarbostyril (240 mg) as white powder, m.p.: 254°-255° C.

Using the suitable starting materials, the compounds of the above Examples 172, 183-186, 233, 236-240, 244, 245 and 347 are obtained in the same manners as in Example 432.

Example 433

To a solution of 1-[4-(1-piperazinylcarbonyl)phenyl]-3,4-dihydrocarbostyril (0.15 g) in dichloromethane (20 ml) is added triethylamine (91 mg), and further thereto is added with stirring a solution of benzoyl chloride (69 mg) in dichloromethane (2 ml) under ice cooling and the mixture is stirred at room temperature for 1 hour. Water is added thereto and the mixture is extracted with dichloromethane, dried with magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is crystallized by adding diethyl ether and n-hexane. The precipitated crystal is recrystallized from ethanol/diethyl ether/n-hexane to give 1-[4-(4-benzoyl-1-piperazinyl)phenyl]-3,4-dihydrocarbostyril (0.16 g) as white powder, m.p.: 188°-189° C.

Using the suitable starting materials, the compound of the above Example 240 is obtained in the same manners as in Example 433.

Example 434

1-{1-[4-(2-Carboxyethyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2 g) is dissolved in methanol (50 ml) and thereto is added dropwise thionyl chloride (1.1 ml) under ice cooling. After adding, the mixture is stirred at 0°-5° C. for 1 hour and further at room temperature overnight. The solvent is concentrated and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1) and recrystallized from n-hexane to give 1-{1-[4-(2-methoxycarbonylethyl)benzoyl]-4-piperidinyl}-3,4-dihyrocarbostyril (1.46 g) as white powder, m.p.: 85°-86° C.

Using the suitable starting materials, the compounds of the above Examples 49, 111, 112, 123, 127, 181, 213, 264, 274, 297, 299, 302, 306, 311, 320, 322, 323, 327, 328 and 342 are obtained in the same manners as in Example 434.

Using the suitable starting materials, the following compounds are obtained in the same manners as in Examples 1 and 384.

                  TABLE 3     ______________________________________      ##STR454##     ______________________________________     Example 435     Structure      ##STR455##     R.sup.1 : F (6-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 210)     Form: Free     Example 436     Structure      ##STR456##     R.sup.1 : F (6-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 135-136° C.     Form: Free     Example 437     Structure      ##STR457##     R.sup.1 : F (5-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 137-140° C.     Form: Free     Example 438     Structure      ##STR458##     R.sup.1 : F (5-, 7-positions, q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 178-180° C.     Form: Free     Example 439     Structure      ##STR459##     R.sup.1 : CH.sub.3 (3-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 211)     Form: Free     Example 440     Structure      ##STR460##     R.sup.1 : CH.sub.3 (3-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 212)     Form: Free     Example 441     Structure      ##STR461##     R.sup.1 : CO.sub.2 C.sub.2 H.sub.5 (3-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 213)     Form: Free     Example 442     Structure      ##STR462##     R.sup.1 : CO.sub.2 C.sub.2 H.sub.5 (3-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 214)     Form: Free     Example 443     Structure      ##STR463##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     NMR analysis: 215)     Form: Free     Example 444     Structure      ##STR464##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/n-hexane     Melting point: 140-143° C.     Form: Free     Example 445     Structure      ##STR465##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 216)     Form: Free     Example 446     Structure      ##STR466##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 217)     Form: Free     Example 447     Structure      ##STR467##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 218)     Form: Free     Example 448     Structure      ##STR468##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 219)     Form: Free     Example 449     Structure      ##STR469##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 208-210° C.     Form: Dioxalate     Example 450     Structure      ##STR470##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Light yellow powders     Recrystallization solvent: n-Hexane/diethyl ether     Melting point: 64-68° C.     Form: Dihydrochloride.trihydrate     Example 451     Structure      ##STR471##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 220)     Form: Free     Example 452     Structure      ##STR472##     R.sup.1 H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 221)     Form: Free     Example 453     Structure      ##STR473##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 222)     Form: Free     Example 454     Structure      ##STR474##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 214-217° C.     Form: Dioxalate     Example 455     Structure      ##STR475##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 208-211° C. (decomposed)     Form: Dioxalate     Example 456     Structure      ##STR476##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 206-210° C.     Form: Dioxalate     Example 457     Structure      ##STR477##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 223)     Form: Free     Example 458     Structure      ##STR478##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 224)     Form: Free     Example 459     Structure      ##STR479##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 225)     Form: Free     Example 460     Structure      ##STR480##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/diethyl ether     Melting point: 123-125° C.     Form: Free     Example 461     Structure      ##STR481##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Light yellow needles     Recrystallization solvent: Ethanol/chloroform     Melting point: 194-196° C.     Form: Free     Example 462     Structure      ##STR482##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 226)     Form: Free     Example 463     Structure      ##STR483##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless prisms     Recrystallization solvent: Ethanol     Melting point: 249-252° C.     Form: Free     Example 464     Structure      ##STR484##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless prisms     Recrystallization solvent: Methanol     Melting point: 107-110° C.     Form: Free     Example 465     Structure      ##STR485##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/diethyl ether     Melting point: 120-122° C.     Form: Free     Example 466     Structure      ##STR486##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 227)     Form: Free     Example 467     Structure      ##STR487##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 228)     Form: Free     Example 468     Structure      ##STR488##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 229)     Form: Free     Example 469     Structure      ##STR489##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 230)     Form: Free     Example 470     Structure      ##STR490##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 231)     Form: Free     Example 471     Structure      ##STR491##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 232)     Form: Free     Example 472     Structure      ##STR492##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 233)     Form: Free     Example 473     Structure      ##STR493##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 234)     Form: Free     Example 474     Structure      ##STR494##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 235)     Form: Free     Example 474A     Structure      ##STR495##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 236)     Form: Free     ______________________________________

                  TABLE 4     ______________________________________     No.      NMR (CDCl.sub.3) δ value     ______________________________________     210      1.60(1H, s), 1.68-1.85(2H, m), 2.35-2.92(8H, m)              3.15-3.32(2H, 4.18-4.40(1H, m), 6.86-7.18              (2H, m)     211      1.21(3H, d, J=6.5Hz), 1.60-2.00(3H, m), 2.35-              2.95(8H, m), 3.14-3.37(2H, m), 4.28-4.50(1H, m)              6.95-7.32(4H, m)     212      1.21(3H, d, J=6.5Hz), 1.42(3H, t, J=7.0Hz),              1.62-2.04(2H, m), 2.30-3.28(7H, m), 3.55-3.95              (4H, m), 4.04(2H, q, J=7.0Hz), 4.25-5.10(2H, m)              6.38-6.60(2H, m), 6.98-7.40(5H, m)     213      1.18(3H, t, J=7.1Hz), 1.50-1.88(3H, m), 2.50-              3.46(9H, m), 3.60-3.62(2H, m), 4.03-4.28(2H, m),              4.47-4.60(1H, m), 6.95-7.30(4H, m)     214      1.17(3H, t, J=7.1Hz), 1.42(3H, t, J=7.0Hz),              1.56-2.00(2H, m), 2.38-3.35(6H, m), 3.42-5.10              (11H, m), 6.37-6.60(2H, m), 6.95-7.40(5H, m)     215      1.58-1.97(2H, m), 2.43-3.22(10H, m), 3.65-5.12              (5H, m), 5.68-5.84, 6.18-6.36(total: 1H, m),              6.51(1H, d, J=15.9Hz), 6.46-7.49(8H, m)     216      1.56-1.98(6H, m), 2.05(3H, s), 2.52-3.21(10H, m)              3.76-5.08(5H, m), 6.98-7.43(8H, m)     217      1.44(3H, t, J=7.5Hz), 1.68-1.97(2H, m), 2.28-              3.17(10H, m), 3.05(2H, q, J=7.5Hz), 3.20(2H, t,              J=7.4Hz), 3.78-5.13(3H, m), 4.15(2H, t, J=5.7              Hz), 6.86-7.49(8H, m)     218      1.44(3H, t, J=7.5Hz), 1.68-1.97(2H, m), 2.28-              3.17(10H, m), 3.05(2H, q, J=7.5Hz), 3.20(2H, t,              J=7.4Hz), 3.78-5.13(3H, m), 4.15(2H, t, J=5.7              Hz), 6.86-7.49(8H, m)     219      1.34-1.93(8H, m), 2.17-2.42(2H, m), 2.31(6H, s),              2.51-3.04(9H, m), 3.62-5.07(6H, m), 6.86-6.95              (2H, m), 6.97-7.32(4H, m), 7.36-7.48(2H, m)     220      1.68-2.18(4H, m), 2.09(3H, s), 3.28-3.13(14H,              m), 3.43-3.72(4H, m), 3.86-5.08(5H, m), 6.85-7.50              (8H, m)     221      1.70-2.08(4H, m), 2.34-3.12(14H, m), 3.34-5.04              (9H, m), 6.88-7.52(8H, m), 7.40(5H, s)     222      1.72-2.14(4H, m), 2.40-3.14(14H, m), 3.43-3.60              (4H, m), 3.73-5.13(5H, m), 6.47(1H, brs), 6.88-              7.48(13H, m)     223      1.71-2.15(6H, m), 2.46-3.20(8H, m), 3.80-5.15              (2H, m), 3.96(4H, t, J=6.8Hz), 4.39(1H, m), 6.15              (2H, t, J=2.1Hz), 6.67(2H, t, J=2.1Hz), 6.88              (2H, d, J=8.7Hz), 6.99-7.28(4H, m), 7.42(2H, d,              J=8.7Hz)     224      1.60-1.98(2H, m), 2.11(2H, quint, J=6.5Hz), 2.36              (2H, t, J=6.5Hz), 2.53-3.15(8H, m), 2.78(3H, d,              J=4.8Hz), 3.60-5.10(2H, brs), 4.00(2H, t, J=6.5              Hz), 4.36(1H, m), 6.16(1H, brs), 6.88(2H, d, J=              8.7Hz), 6.99-7.29(4H, m), 7.41(2H, d, J=8.7Hz)     225      1.33(3H, t, J=6.8Hz), 1.65-1.94(2H, m), 2.14              (2H, quint, J=6.6Hz), 2.37(2H, t, J=6.6Hz),              2.46-3.12(8H, m), 3.80-5.00(2H, m), 4.03(2H, t,              J=6.6Hz), 4.05(2H, q, J=6.8Hz), 4.38(1H, m),              5.69(1H, brs), 6.90(2H, d, J=8.6Hz), 6.98-7.30              (4H, m), 7.42(2H, d, J=8.6Hz)     226      1.63-1.92(2H, m), 2.40-3.80(10H, m), 4.08-4.55              (3H, m), 6.41(1H, brs), 6.52-6.75(2H, m), 6.92-              7.35(6H, m),     227      1.31-2.02(10H, m), 2.47-3.25(10H, m), 2.95(3H,              s), 3.98(2H, t, J=6.3Hz), 4.04-5.05(4H, m), 6.89              (2H, d, J=8.8Hz), 6.95-7.37(4H, m), 7.42(2H, d,              J=8.8Hz),     228      1.25-2.18(13H, m), 2.45-3.40(10H, m), 3.97(2H,              t, J=6.4Hz), 4.05-5.07(3H, m), 5.79(1H, brs),              6.89(2H, d, J=8.7Hz), 6.95-7.37(4H, m), 7.42              (2H, d, J=8.7Hz)     229      1.60-2.05(6H, m), 2.43-3.15(8H, m), 3.34(3H, s),              3.49-3.63(2H, m), 3.82-5.05(5H, m), 5.17(2H, s),              6.50(1H, brs), 6.88(2H, d, J=8.6Hz), 6.94-7.49              (13H, m), 7.74(2H, d, J=8.6Hz)     230      1.60-2.07(6H, m), 2.42-3.18(11H, m), 3.35-3.62              (2H, m), 3.80-5.09(6H, m), 6.20-6.45(1H, m), 6.54              (2H, d, J=8.7Hz), 6.88(2H, d, J=8.7Hz), 6.94-              7.35(4H, m), 7.40(2H, d, J=8.7Hz), 7.63(2H, d,              J=8.7Hz)     231      1.45-1.99(8H, m), 2.48-3.18(8H, m), 3.99(2H, t,              J=6.3Hz), 4.10(2H, t, J=6.3Hz), 4.17-5.08(5H,              m), 6.82-7.54(8H, m)     232      1.27-1.99(10H, m), 2.40-3.15(8H, m), 3.70(2H, t,              J=7Hz), 3.97(2H, t, J=6.3Hz), 4.08-5.10(3H, m),              6.29-7.96(12H, m)     233      1.26-1.95(10H, m), 2.05(3H, s), 2.45-3.18(8H,              m), 3.87-5.08(7H, m), 6.82-7.52(8H, m)     234      1.25-2.03(12H, m), 2.45-3.26(10H, m), 3.98(2H,              t, J=6.4Hz), 4.08-5.11(3H, m), 6.90(2H, d, J=8.8              Hz), 6.90-7.39(4H, m), 7.42(2H, d, J=8.8Hz)     235      1.63-2.22(6H, m), 2.47-3.18(8H, m), 3.63(2H, t,              J=6.6Hz), 3.94-5.04(5H, m), 6.82-7.52(8H, m)     236      1.11(6H, t, J=7.2Hz), 1.35-1.96(8H, m), 2.32-              3.13(14H, m), 3.58-5.07(5H, m), 4.00(2H, t,              J=6.3Hz), 6.83-6.95(2H, m), 6.98-7.32(4H, m),              7.35-7.48(2H, m),     ______________________________________

The following compound is obtained in the same manners as in Examples 1 and 385.

                  TABLE 5     ______________________________________      ##STR496##     ______________________________________     Example 475     Structure      ##STR497##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/diethyl ether     Melting point: 144-146° C.     Form: Free     ______________________________________

Example 476

To a solution of 1-{1-[4-(3-ethylthiopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.44 g) in dichloromethane (10 ml) is added m-chloroperbenzoic acid (0.52 g) under ice cooling. The mixture is stirred at room temperature overnight, and the reaction mixture is poured into aqueous sodium carbonate solution. The mixture is extracted with chloroform and dried with sodium carbonate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:2) to give 1-{1-[4-(3-ethylsulfonylpropoxy)benzoyl]-4-piperidinyl)-3,4-dihydrocarbostyril (0.19 g).

NMR (CDCl₃) δ ppm: 1.44 (3H, t, J=7.5 Hz), 1.68-1.97 (2H, m), 2.28-3.17 (10H, m), 3.05 (2H, q, J=7.5 Hz), 3.20 (2H, t, J=7.4 Hz), 3.78-5.13 (3H, m), 4.15 (2H, t, J=5.7 Hz), 6.86-7.49 (8H, m)

Example 478

A mixture of 1-{1-[4-(4-aminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.50 g), acetic acid (10 ml) and 2,5-dimethoxytetrahydrofuran (0.17 ml) is refluxed with stirring under heating for 1 hour. The reaction solution is concentrated under reduced pressure and the resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=100:1) to give 1-[1-{4-[4-(1-pyrrolyl)butoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (0.30 g).

NMR (CDCl₃) δ ppm: 1.71-2.15 (6H, m), 2.46-3.20 (8H, m), 3.80-5.15 (2H, m), 3.96 (4H, t, J=6.8 Hz), 4.39 (1H, m), 6.15 (2H, t, J=2.1 Hz), 6.67 (2H, t, J=2.1 Hz), 6.88 (2H, d, J=8.7 Hz), 6.99-7.28 (4H, m), 7.42 (2H, d, J=8.7 Hz)

Example 479

Sodium metaperiodate (0.28 g) is dissolved in water (4 ml) and thereto is added a solution of 1-{1-[4-(3-ethylthiopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.4 g) in methanol (15 ml) and the mixture is stirred at room temperature overnight. The reaction mixture is concentrated and the residue is extracted with chloroform. The extract is dried with magnesium sulfate and the solvent is distilled off. The resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:2→ethyl acetate:methanol=20:1) to give 1-{1-[4-(3-ethylsulfinylpropoxy)benzoyl]-4-piperidinyl]-3,4-dihydrocarbostyril (0.12 g).

NMR (CDCl₃) δ ppm: 1.44 (3H, t, J=7.5 Hz), 1.68-1.97 (2H, m), 2.28-3.17 (10H, m), 3.05 (2H, q, J=7.5 Hz), 3.20 (2H, t, J=7.4 Hz), 3.78-5.13 (3H, m), 4.15 (2H, t, J=5.7 Hz), 6.86-7.49 (8H, m)

Example 480

4-Hydroxypropyltriphenylphosphonium bromide (2.4 g) is dispersed into tetrahydrofuran (50 ml) and thereto is added dropwise lithium diisopropylamide (a solution in 1.99N tetrahydrofuran) (6.1 ml) at 0°-5° C. After adding, the mixture is stirred at 0°-5° C. for 1 hour and thereto is added 1-[1-(4-formylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril (2 g). The mixture is stirred at room temperature overnight. The reaction mixture is poured into ice-water and adjusted to pH 4-5 by adding conc. hydrochloric acid. The mixture is extracted with ethyl acetate and dried with magnesium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (solvent: n-hexane:ethyl acetate=1:1→ethyl acetate:methanol=20:1) to give 1-{1-[4-(4-hydroxy-1-butenyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1 g).

NMR (CDCl₃) δ ppm: 1.58-1.97 (2H, m), 2.43-3.22 (10H, m), 3.65-5.12 (5H, m), 5.68-5.84, 6.18-6.36 (total; 1H, m), 6.51 (1H, d, J=15.9 Hz), 6.96-7.49 (8H, m)

Example 481

To crushed aluminum chloride (26 g) are added chlorobenzene (26 ml) and N-cinnamoyl-N-(1-benzoyl-4-piperidinyl)aniline (8.7 g) and the mixture is reacted at 110° C. for 1 hour. After cooling, the reaction mixture is poured into ice-water and the mixture is basified with aqueous sodium hydroxide solution. The mixture is extracted with dichloromethane and the solvent is concentrated. The residue is purified by silica gel column chromatography (solvent: methylene chloride) to give 1-(1-benzoyl-4-piperidinyl)carbostyril (5.9 g).

Using the suitable starting materials, the compounds of the above Examples 10, 166-168, 475 and the following Examples 578-587 are obtained in the same manners as in Example 481.

Using the suitable materials, the following compounds are obtained in the same manners as in Exampels 1 and 384.

                                      TABLE 6     __________________________________________________________________________      ##STR498##     __________________________________________________________________________     Example 482     Structure      ##STR499##     R.sup.1 : COOH (3-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 237)     Form: Free     Example 483     Structure      ##STR500##     R.sup.1 : CONHNH.sub.2 (3-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 238)     Form: Free     Example 484     Structure      ##STR501##      ##STR502##     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 239)     Form: Free     Example 485     Structure      ##STR503##     R.sup.1 : NH.sub.2 (3-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Melting point: 257-260° C.     Form: Hydrochloride     Example 486     Structure      ##STR504##     R.sup.1 : NHCOCH.sub.3 (3-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 240)     Form: Free     Example 487     Structure      ##STR505##     R.sup.1 : N(CH.sub.3).sub.2 (3-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 241)     Form: Free     Example 488     Structure      ##STR506##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 242)     Form: Free     Example 489     Structure      ##STR507##     R.sup.1 : F (5-, 7-position), q: 2     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 245)     Form: Free     Example 490     Structure      ##STR508##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 246)     Form: Free     Example 491     Structure      ##STR509##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 247)     Form: Free     Example 492     Structure      ##STR510##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 248)     Form: Free     Example 493     Structure      ##STR511##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 249)     Form: Free     Example 494     Structure      ##STR512##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 250)     Form: Free     Example 495     Structure      ##STR513##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 251)     Form: Free     Example 496     Structure      ##STR514##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 252)     Form: Free     Example 497     Structure      ##STR515##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 253)     Form: Free     Example 498     Structure      ##STR516##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 254)     Form: Free     Example 499     Structure      ##STR517##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 255)     Form: Free     Example 500     Structure      ##STR518##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 256)     Form: Free     Example 501     Structure      ##STR519##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 257)     Form: Free     Example 502     Structure      ##STR520##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 258)     Form: Free     Example 503     Structure      ##STR521##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 259)     Form: Free     Example 504     Structure      ##STR522##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 260)     Form: Free     Example 505     Structure      ##STR523##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 261)     Form: Free     Example 506     Structure      ##STR524##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 262)     Form: Free     Example 507     Structure      ##STR525##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 263)     Form: Free     Example 508     Structure      ##STR526##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 264)     Form: Free     Example 509     Structure      ##STR527##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 265)     Form: Free     Example 510     Structure      ##STR528##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 266)     Form: Free     Example 511     Structure      ##STR529##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 267)     Form: Free     Example 512     Structure      ##STR530##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     NMR analysis: 268)     Recrystallization solvent: Ethyl acetate/n-hexane     Melting point: 121-126° C.     Form: Free     Example 513     Structure      ##STR531##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 269)     Form: Free     Example 514     Structure      ##STR532##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 270)     Form: Free     Example 515     Structure      ##STR533##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powder     Recrystallization solvent: Ethyl acetate/n-hexane     Melting point: 175.5-177° C.     Form: Free     Example 516     Structure      ##STR534##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 271)     Form: Free     Example 517     Structure      ##STR535##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 272)     Form: Free     Example 518     Structure      ##STR536##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 273)     Form: Free     Example 519     Structure      ##STR537##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 274)     Form: Free     Example 520     Structure      ##STR538##     R.sup.1 : H, q: =1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 275)     Form: Free     Example 521     Structure      ##STR539##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 276)     Form: Free     Example 522     Structure      ##STR540##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 277)     Form: Free     Example 523     Structure      ##STR541##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 278)     Form: Free     Example 524     Structure      ##STR542##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 279)     Form: Free     Example 525     Structure      ##STR543##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 196-198° C.     Form: Dioxalate     Example 526     Structure      ##STR544##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 214-215° C.     Form: Dioxalate     Example 527     Structure      ##STR545##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 280)     Form: Free     Example 528     Structure      ##STR546##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 281)     Form: Free     Example 529     Structure      ##STR547##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 282)     Form: Free     Example 530     Structure      ##STR548##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 283)     Form: Free     Example 531     Structure      ##STR549##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 284)     Form: Free     Example 532     Structure      ##STR550##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 285)     Form: Free     Example 533     Structure      ##STR551##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 286)     Form: Free     Example 534     Structure      ##STR552##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 196-198° C.     Form: Dioxalate     Example 535     Structure      ##STR553##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 198-199° C.     Form: Dioxalate     Example 536     Structure      ##STR554##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 287)     Form: Free     Example 537     Structure      ##STR555##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 288)     Form: Free     Example 538     Structure      ##STR556##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 289)     Form: Free     Example 539     Structure      ##STR557##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 290)     Form: Free     Example 540     Structure      ##STR558##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 291)     Form: Free     Example 541     Structure      ##STR559##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 292)     Form: Free     Example 542     Structure      ##STR560##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 293)     Form: Free     Example 543     Structure      ##STR561##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 294)     Form: Free     Example 544     Structure      ##STR562##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 295)     Form: Free     Example 545     Structure      ##STR563##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 296)     Form: Free     Example 546     Structure      ##STR564##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 297)     Form: Free     Example 547     Structure      ##STR565##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 298)     Form: Free     Example 548     Structure      ##STR566##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 299)     Form: Free     Example 549     Structure      ##STR567##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 300)     Form: Free     Example 550     Structure      ##STR568##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 301)     Form: Free     Example 551     Structure      ##STR569##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 302)     Form: Free     Example 552     Structure      ##STR570##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 303)     Form: Free     Example 553     Structure      ##STR571##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 304)     Form: Free     Example 554     Structure      ##STR572##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 305)     Form: Free     Example 555     Structure      ##STR573##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 306)     Form: Free     Example 556     Structure      ##STR574##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 307)     Form: Free     Example 557     Structure      ##STR575##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 308)     Form: Free     Example 558     Structure      ##STR576##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 309)     Form: Free     Example 559     Structure      ##STR577##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 310)     Form: Free     Example 560     Structure      ##STR578##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 311)     Form: Free     Example 561     Structure      ##STR579##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 312)     Form: Free     Example 562     Structure      ##STR580##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 313)     Form: Free     Example 563     Structure      ##STR581##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 314)     Form: Free     Example 564     Structure      ##STR582##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 315)     Form: Free     Example 565     Structure      ##STR583##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 316)     Form: Free     Example 566     Structure      ##STR584##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 317)     Form: Free     Example 567     Structure      ##STR585##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     NMR analysis: 318)     Form: Free     Example 568     Structure      ##STR586##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 319)     Form: Free     Example 569     Structure      ##STR587##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 320)     Form: Free     Example 570     Structure      ##STR588##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 321)     Form: Free     Example 571     Structure      ##STR589##     R.sup.1 : F (5-, 7-position), q: 2     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 325)     Form: Free     Example 572     Structure      ##STR590##     R.sup.1 : F (5-, 7-position), q: 2     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 326)     Form: Free     Example 573     Structure      ##STR591##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 63-65° C.                 Form: Free     Example 574     Structure      ##STR592##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 138-140° C.                 Form: Free     Example 575     Structure      ##STR593##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 83-86° C.                 Form: Free     Example 576     Structure      ##STR594##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 140-142° C.                 Form: Free     Example 577     Structure      ##STR595##     R.sup.1 : CH.sub.3 (5-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 327)     Form: Free     Example 577A     Structure      ##STR596##     R.sup.1 : CH.sub.3 (5-position), q: 1     Bond between 3- and 4-positions in the carbostyril ring: Single bond     Crystalline form: White amorphous form     NMR analysis: 328)     Form: Free     __________________________________________________________________________

The following compounds are obtained in the same manners as in examples 1 and 385.

                  TABLE 7     ______________________________________      ##STR597##     ______________________________________     Example 578     Structure      ##STR598##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the     carbostyryl ring: Double bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 182-185° C.     Form: Free     Example 579     Structure      ##STR599##     R.sup.1 : F (5-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White powders     Recrystallization solvent: Ethanol     Melting point: 183-185° C.     Form: Free     Example 580     Structure      ##STR600##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White amorphous form     NMR analysis: 243)     Form: Free     Example 581     Structure      ##STR601##     R.sup.1 : R (5-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/n-hexane     Melting point: 186-187° C.     Form: Free     Example 582     Structure      ##STR602##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/diethyl ether     Melting pint: 187-188° C. Form: Free     Example 583     Structure      ##STR603##     R.sup.1 : F (7-position), q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White amorphous form     NMR analysis: 244)     Form: Free     Example 584     Structure      ##STR604##     R.sup.1 : F( 5-, 7-positions), q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/diethyl ether     Melting point: 150-152° C.     Form: Free     Example 585     Structure      ##STR605##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White amorphous form     NMR analysis: 322)     Form: Free     Example 586     Structure      ##STR606##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White amorphous form     NMR analysis: 323)     Form: Free     Example 587     Structure      ##STR607##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Double bond     Crystalline form: White amorphous form     NMR analysis: 324)     Form: Free     ______________________________________

                  TABLE 8     ______________________________________     No.      NMR (CDCl.sub.3) δ value     ______________________________________     237      1.42(3H, t, J=7.0Hz), 1.58-2.05(2H, m), 2.35-              3.47(7H, m), 3.55-3.95(4H, m), 4.04(2H, q, J=7              Hz), 4.38(1H, brs), 4.94(1H, brs), 6.37-6.56(2H,              m), 7.00-7.40(5H, m)     238      1.42(3H, t, J=7Hz), 1.52-1.95(2H, m), 2.30-3.93              (13H, m), 4.04(2H, q, J=7Hz), 4.15-5.06(3H, m),              6.40-6.62(2H, m), 6.97-7.50(5H, m)     239      1.40(3H, t, J=7Hz), 1.55-2.00(2H, m), 2.30-5.05              (15H, m), 5.30(2H, s), 5.95(1H, brs), 6.50-6.60              (2H, m), 7.02-7.42(10H, m)     240      1.42(3H, t, J=7Hz), 1.55-1.98(2H, m), 2.08(3H,              s), 2.40-3.95(7H, m), 4.05(2H, q, J=7Hz), 4.20-              4.65(2H, m), 4.90-5.11(1H, m), 6.42-6.73(3H, m),              7.02-7.40(5H, m)     241      1.42(3H, t, J=7Hz), 1.50-1.96(2H, m), 2.43(6H,              s), 2.51-3.28(7H, m), 3.57-3.95(4H, m), 4.04(2H,              q, J=7Hz), 4.33-4.75(1H, m), 4.84-5.06(1H, m),              6.40-6.60(2H, m), 6.99-7.32(5H, m)     242      1.68-2.15(4H, m), 2.45-3.20(8H, m), 3.40-3.62              (2H, m), 4.06(2H, t, J=5.9Hz), 4.10-5.10(3H, m),              6.26(1H, brs), 6.68-7.25(5H, m), 7.42(2H, d,              J=8.7Hz), 8.15(1H, s)     243      1.65-1.88(2H, m), 2.20(1H, brs), 2.60-3.05(4H,              m), 3.18-3.42(2H, m), 5.15(1H, brs), 6.59(1H, d,              J=9.4Hz), 6.94(1H, m), 7.35-7.65(3H, m)     244      1.60-1.97(2H, m), 2.50-3.33(4H, m), 3.54-4.02              (7H, m), 4.95-5.12(1H, m), 6.40-6.65(3H, m),              6.90-7.13(1H, m), 7.15-7.67(4H, m)     245      1.08(6H, t, J=7.1Hz), 1.32-1.90(8H, m), 2.25-              3.20(15H, m), 3.60-5.10(9H, m), 6.40-6.85(4H,              m), 7.15-7.30(1H, m)     246      1.45-1.97(6H, m), 2.16(2H, m), 2.36-3.32(8H, m),              2.56(2H, m), 3.60-5.15(2H, m), 3.87(2H, m), 4.32              (2H, m), 4.68(2H, m), 6.19(1H, brs), 6.64(2H, d,              J=8.0Hz), 6.83(2H, d, J=8.3Hz), 6.92-7.23(8H,              m), 7.36(2H, d, J=8.3Hz)     247      0.95(3H, d, J=6.0Hz), 0.98(3H, d, J=6.0Hz),              1.38-1.61(2H, m), 1.62-1.96(6H, m), 2.08(1H, m),              2.27(2H, t, J=7.3Hz), 2.53-3.15(8H, m), 3.77-              4.85(2H, m), 3.97(2H, t, J=6.2Hz), 4.32(2H, m),              5.79(1H, brs), 6.50(2H, m), 6.89(2H, d, J=8.6              Hz), 6.99-7.27(4H, m), 7.42(2H, d, J=8.6Hz)     248      1.67-1.96(2H, m), 2.14(2H, quint, J=6.3Hz),              2.40-3.10(8H, m), 2.52(2H, t, J=6.3Hz), 2.96              (3H, s), 3.02(3H, s), 3.85-5.10(2H, m), 4.07(2H,              t, J=6.3Hz), 4.37(1H, m), 6.92(2H, d, J=8.6Hz),              6.98-7.33(4H, m), 7.43(2H, d, J=8.6Hz),     249      1.65-1.95(2H, m), 2.12(2H, quint, J=6.4Hz),              2.41(2H, t, J=6.4Hz), 2.54-2.85(8H, m), 3.80-              5.10(2H, m), 3.98(2H, t, J=6.4Hz), 4.35(1H, m),              4.40(2H, d, J=5.5Hz), 6.54-6.92(1H, brs), 6.83              (2H, d, J=8.6Hz), 6.99-7.31(9H, m), 7.37(2H, d,              J=8.6Hz)     ______________________________________     No.      NMR (DMSO-d.sub.6) δ value     ______________________________________     250      1.21-1.82(8H, m), 2.08(2H, t, J=7.1Hz), 2.26-              3.20(8H, m), 3.39(2H, m), 3.60-4.66(2H, brs),              3.93(2H, t, J=6.4Hz), 4.32(2H, m), 6.71(1H, s),              6.84-7.01(2H, brs), 6.94(2H, d, J=8.7Hz), 7.16-              7.31(4H, m), 7.32(2H, d, J=8.7Hz), 7.47(1H, s),              7.88(1H, d, J=8.2Hz),     251      1.10-1.97(10H, m), 2.07(2H, t, J=7.6Hz), 2.16              (2H, t, J=7.3Hz), 2.32-3.40(8H, m), 3.60-4.80              (2H, brs), 3.99(2H, t, J=6.4Hz), 4.15(1H, m),              4.28(1H, m), 6.74(1H, brs), 6.98(2H, d, J=8.6              Hz), 7.05(1H, brs), 7.20-7.29(4H, m), 7.36(2H,              d, J=8.6Hz), 7.85(1H, d, J=7.7Hz)     ______________________________________     No.      NMR (CDCl.sub.3) δ value     ______________________________________     252      1.38-1.59(2H, m), 1,60-2.18(8H, m), 2.09(3H, s),              2.25(2H, t, J=7.2Hz), 2.44-3.17(8H, m), 2.57              (2H, t, J=6.1Hz), 3.55-5.10(2H, brs), 3.97(2H,              t, J=6.1Hz), 4.38(1H, m), 4.64(1H, q, J=7.2Hz),              5.95(1H, brs), 6.78(1H, brs), 6.82(1H, brs),              6.89(2H, d, J=8.7Hz), 6.91-7.28(4H, m), 7.41              (2H, d, J=8.7Hz)     253      1.42-1.64(2H, m), 1.64-2.06(6H, m), 2.57(2H, t,              J=6.1Hz), 2.64-3.24(8H, m), 3.67-5.15(2H, m),              3.92(2H, t, J=6.1Hz), 4.34(1H, m), 6.84(2H, d,              J=8.7Hz), 7.00-7.36(5H, m), 7.40(2H, d, J=8.7              Hz), 8.28(1H, d, J=5.6Hz), 8.80(1H, s)     254      1.13-1.96(14H, m), 2.25(2H, t, J=7.3Hz), 2.46-              3.08(8H, m), 3.16(2H, m), 3.72(3H, s), 3.96(2H,              t, J=6.2Hz), 4.05-4.97(2H, m), 4.37(1H, m), 4.57              (1H, m), 5.07(1H, brs), 5.08(2H, s), 6.34(1H, d,              J=7.5Hz), 6.88(2H, d, J=8.6Hz), 6.98-7.30(4H,              m), 7.34(5H, s), 7.41(2H, d, J=8.6Hz)     255      1.30-1.93(14H, m), 2.27(2H, t, J=7.3Hz), 2.53-              3.11(10H, m), 3.73(3H, s), 3.98(2H, t, J=6.3              Hz), 4.13-5.06(2H, m), 4.38(1H, m), 4.59(1H, m),              6.46(1H, d, J=7.8Hz), 6.89(2H, d, J=8.6Hz),              6.98-7.30(4H, m), 7.42(2H, d, J=8.6Hz)     256      1.14(3H, t, J=7.6Hz), 1.84(2H, m), 2.00(2H,              quint, J=6.1Hz), 2.21(2H, q, J=7.6Hz), 2.43-3.23              (8H, m), 3.42(2H, q, J=6.1Hz), 3.65-5.14(2H, m),              4.03(2H, t, J=6.1Hz), 4.36(1H, m), 6.52(1H,              brs), 6.89(2H, d, J=8.4Hz), 6.98-7.32(4H, m),              7.42(2H, d, J=8.4Hz)     257      0.95(6H, t, J=6.3Hz), 1.84(2H, m), 1.94-2.22              (5H, m), 2.53-3.17(8H, m), 3.46(2H, q, J=6.1Hz),              3.66-5.05(2H, m), 4.05(2H, t, J=6.1Hz), 4.38              (1H, m), 6.00(1H, brs), 6.90(2H, d, J=8.7Hz),              6.99-7.29(4H, m), 7.43(2H, d, J=8.7Hz)     258      1.24(3H, t, J=7.1Hz), 1.66-1.93(2H, m), 2.01              (2H, quint, J=6.2Hz), 2.53-3.15(8H, m), 3.39(2H,              q, J=6.2Hz), 3.60-5.10(2H, m), 4.05(2H, t, J=6.2              Hz), 4.11(2H, q, J=7.1Hz), 4.39(1H, m), 4.94              (1H, brs), 6.91(2H, d, J=8.7Hz), 6.98-7.29(4H,              m), 7.43(2H, d, J=8.7Hz)     259      0.92(6H, d, J=6.7Hz), 1.60-1.94(3H, m), 2.02              (2H, quint, J=6.2Hz), 2.53-3.15(8H, m), 3.39(2H,              q, J=6.2Hz), 3.60-5.20(2H, m), 3.84(2H, d, J=6.7              Hz), 4.06(2H, t, J=6.2Hz), 4.39(1H, m), 4.95              (1H, brs), 6.91(2H, d, J=8.7Hz), 6.98-7.29(4H,              m), 7.43(2H, d, J=8.7Hz)     260      1.55-1.87(2H, m), 1.95(2H, quint, J=6.0Hz),              2.52-3.10(8H, m), 3.12(2H, q, J=6.0Hz), 3.66-              5.10(2H, m), 3.96(2H, t, J=6.0Hz), 4.37(1H, m),              5.51(1H, brs), 6.81(2H, d, J=8.6Hz), 6.98-7.30              (4H, m), 7.36-7.60(5H, m), 7.85(2H, d, J=8.6Hz)     261      1.60-1.90(2H, m), 1.95(2H, quint, J=6.1Hz), 2.40              (3H, s), 2.50-3.10(8H, m), 3.15(2H, q, J=6.1Hz),              3.70-5.05(2H, m), 3.97(2H, t, J=6.1Hz), 4.38              (1H, m), 5.19(1H, t, J=6.1Hz), 6.82(2H, d, J=8.7              Hz), 6.98-7.28(4H, m), 7.27(2H, d, J=8.7Hz),              7.40(2H, d, J=8.7Hz), 7.74(2H, d, J=8.1Hz),     262      1.68-1.93(2H, m), 1.93-2.14(2H, m), 2.02(3H, s),              2.53-3.25(8H, m), 3.46(2H, q, J=5.9Hz), 3.70-              5.15(2H, m), 3.86(2H, d, J=4.6Hz), 4.04(2H, t,              J=5.9Hz), 4.37(1H, m), 6.65(1H, brs), 6.77(1H,              brs), 6.90(2H, d, J=8.6Hz), 6.98-7.33(4H, m),              7.42(2H, d, J=8.6Hz)     263      0.93(6H, d, J=6.7Hz), 1.60-1.92(2H, m), 1.93-              2.15(3H, m), 2.00(3H, s), 2.33-3.24(8H, m), 3.45              (2H, m), 3.70-5.10(2H, m), 4.03(2H, t, J=5.9Hz),              4.24(1H, t, J=8.5Hz), 4.38(1H, m), 6.63(1H, d,              J=8.5Hz), 6.89(2H, d, J=8.6Hz), 6.98-7.29(5H,              m), 7.42(2H, d, J=8.6Hz)     264      1.67-1.94(2H, m), 2.04(2H, quint, J=6.2Hz),              2.53-3.20(8H, m), 3.51(2H, q, J=6.2Hz), 3.65-              5.15(2H, m), 4.06(2H, t, J=6.2Hz), 4.37(1H, m),              6.29(1H, brs), 6.91(2H, d, J=8.7Hz), 6.98-7.29              (4H, m), 7.43(2H, d, J=8.7Hz), 8.14(1H, s)     265      1.39-1.62(2H, m), 1.62-1.95(8H, m), 2.20(2H, t,              J=7.4Hz), 2.33(6H, s), 2.50(2H, t, J=6.5Hz),              2.56-3.20(8H, m), 3.34(2H, q, J=5.9Hz), 3.66              (1H, brs), 3.86-5.20(1H, m), 3.98(2H, t, J=6.3              Hz), 4.39(1H, m), 6.89(2H, d, J=8.6Hz), 6.98-              7.30(5H, m), 7.42(2H, d, J=8.6Hz)     266      1.82(2H, m), 2.13(2H, quint, J=5.9Hz), 2.52-3.20              (8H, m), 3.66(2H, q, J=5.9Hz), 3.80-5.10(2H, m),              4.08(2H, t, J=5.9Hz), 4.31(1H, m), 6.86(2H, d,              J=8.7Hz), 6.99-7.12(2H, m), 7.16-7.29(2H, m),              7.38(2H, d, J=8.7Hz), 7.59(1H, t, J=.5.9Hz),              7.98(2H, dd, J=7.0, 1.9Hz), 8.20(2H, dd, J=7.0,              1.9Hz)     267      1.67-1.94(2H, m), 2.09(2H, quint, J=6.0Hz),              2.53-3.20(8H, m), 3.46-5.00(4H, m), 3.60(2H, q,              J=6.0Hz), 4.08(2H, t, J=6.0Hz), 4.34(1H, m),              6.63(2H, d, J=8.6Hz), 6.77(1H, t, J=6.0Hz),              6.88(2H, d, J=8.7Hz), 6.98-7.29(4H, m), 7.39              (2H, d, J=8.7Hz), 7.60(2H, d, J=8.6Hz)     268      1.60-2.33(4H, m), 2.53-3.20(8H, m), 3.30(2H, m),              3.70-5.17(2H, m), 3.91(2H, t, J=5.9Hz), 4.33              (1H, m), 5.83(1H, brs), 6.82(2H, d, J=8.6Hz),              6.92-7.50(9H, m), 7.37(2H, d, J=8.6Hz), 7.67              (1H, s)     269      1.70-2.12(4H, m), 2.00(3H, s), 2.14-2.50(4H, m),              2.53-3.20(8H, m), 3.44(2H, q, J=5.9Hz), 3.80-              5.10(2H, brs), 4.03(2H, t, J=5.9Hz), 4.41(2H,              m), 6.05(1H, brs), 6.70(1H, brs), 6.91(2H, d,              J-8.6Hz), 6.98-7.32(5H, m), 7.41(2H, d, J=8.6              Hz), 7.51(1H, t, J=5.9Hz)     270      1.66-1.97(2H, m), 2.04-2.30(2H, m), 2.15(3H, s),              2.44-3.20(8H, m), 3.60(2H, q, J=5.7Hz), 4.05              (2H, t, J=5.7Hz), 4.31(1H, m), 3.80-5.14(2H, m),              6.82(2H, d, J=8.7Hz), 6.99-7.42(5H, m), 7.31              (2H, d, J=8.7Hz), 7.54(2H, d, J=8.6Hz), 7.69              (2H, d, J=8.6Hz), 8.96(1H, brs)     271      1.06(3H, t, J=6.8Hz), 1.84(2H, m), 1.92(2H,              quint, J=5.9Hz), 2.25-3.20(8H, m), 3.15(2H,              quint, J=6.8Hz), 3.30(2H, q, J=5.9Hz), 3.56-5.10              (2H, m), 4.00(2H, t, J=5.9Hz), 4.33(1H, m), 5.29              (1H, t, J=6.8Hz), 5.67(1H, t, J=5.9Hz), 6.89              (2H, d, J=8.4Hz), 6.98-7.32(4H, m), 7.39(2H, d,              J=8.4Hz)     272      1.40-1.62(2H, m), 1.62-1.94(6H, m), 2.23(2H, t,              J=7.6Hz), 2.27(6H, s), 2.46(2H, t, J=5.8Hz),              2.52-3.10(8H, m), 3.34(2H, q, J=5.8Hz), 3.75-              5.10(2H, m), 3.98(2H, t, J=6.3Hz), 4.38(1H, m),              6.33(1H, brs), 6.94(2H, d, J=8.7Hz), 6.98-7.30              (4H, m), 7.42(2H, d, J=8.7Hz),     273      1.35-1.60(4H, m), 1.61-2.00(8H, m), 2.03-2.21              (4H, m), 2.53-3.14(10H, m), 3.50(2H, s), 3.60-              5.20(2H, m), 3.83(1H, m), 3.97(2H, t, J=6.3Hz),              4.39(1H, m), 5.41(1H, d, J=8.0Hz), 6.88(2H, d,              J=8.7Hz), 6.99-7.32(4H, m), 7.30(5H, m), 7.42              (2H, d, J=8.7Hz)     274      1.70-2.20(6H, m), 1.99(3H, s), 2.08(3H, s),              2.35-3.20(10H, m), 3.45(2H, q, J=6.0Hz), 3.70-              5.20(2H, m), 4.03(2H, t, J=6.0Hz), 4.38(1H, m),              4.57(1H, q, J=7.2Hz), 6.58(1H, d, J=6.0Hz),              6.80-6.98(1H, brs), 6.91(2H, d, J=8.6Hz), 6.99-              7.29(4H, m), 7.43(2H, d, J=8.6Hz)     275      1.70-2.03(4H, m), 2.05(3H, s), 2.58-3.22(8H, m),              2.99(2H, d, J=7.0Hz), 3.44(2H, d, J=5.9Hz),              3.55-5.30(2H, m), 3.96(2H, t, J=5.9Hz), 4.40              (1H, m), 4.72(1H, q, J=7.0Hz), 6.75(1H, s), 6.92              (2H, d, J=8.6Hz), 7.04-7.60(7H, m), 7.44(2H, d,              J=8.6Hz)     276      1.33(3H, d, J=7.0Hz), 1.65-1.93(2H, m), 1.93-              2.12(2H, m), 1.97(3H, s), 2.53-3.20(8H, m), 3.43              (2H, q, J=6.1Hz), 3.80-5.20(2H, m), 4.02(2H, t,              J=6.1Hz), 4.37(1H, m), 4.46(1H, quint, J=7.0              Hz), 6.64(1H, brs), 6.90(2H, d, J=8.7Hz), 6.98-              7.29(5H, m), 7.42(2H, d, J=8.7Hz)     277      1.38-1.64(4H, m), 1.65-2.10(8H, m), 2.20(2H, t,              J=7.3Hz), 2.53-3.10(10H, m), 3.10-3.39(2H, m),              3.45-5.20(2H, m), 3.94(1H, m), 3.98(2H, t, J=6.3              Hz), 4.37(1H, m), 5.82(1H, d, J=7.8Hz), 6.90              (2H, d, J=8.7Hz), 6.98-7.28(4H, m), 7.41(2H, d,              J=8.7Hz)     278      1.85(4H, m), 2.54-3.24(10H, m), 3.35(2H, m),              3.63-5.00(2H, m), 3.85(2H, m), 4.31(2H, m), 5.11              (2H, s), 5.41(1H, brs), 6.15(1H, brs), 6.45(2H,              d, J=8.3Hz), 6.77(2H, d, J=8.6Hz), 6.84(2H, d,              J=8.3Hz), 7.00-7.30(4H, m), 7.34(5H, s), 7.37              (2H, d, J=8.6Hz), 8.12(1H, s)     279      1.57-1.92(6H, m), 2.19-3.15(18H, m), 3.51-3.61              (2H, m), 3.84-5.22(3H, m), 3.99(2H, t, J=6.3Hz),              6.83-7.46(13H, m)     280      1.57-2.05(6H, m), 2.40-3.56(21H, m), 3.73-5.12              (3H, m), 4.02(2H, t, J=5.9Hz), 6.83-7.52(8H, m)     281      1.59-1.98(6H, m), 2.32-3.16(14H, m), 3.35-5.18              (7H, m), 3.70(3H, s), 4.01(2H, t, J=6.2Hz),              6.83-7.48(8H, m)     282      1.66-2.12(6H, m), 2.32-3.13(12H, m), 3.33-5.10              (13H, m), 6.84-7.49(13H, m)     283      1.57-1.95(6H, m), 2.09(3H, s), 2.28-3.28(14H,              m), 3.48-5.07(7H, m), 4.01(2H, t, J=6.2Hz),              6.87-7.49(8H, m)     284      1.71-1.98(6H, m), 2.15(1H, brs), 2.49-3.16(12H,              m), 3.32-5.12(11H, m), 6.85-7.48(8H, m)     285      1.34-2.01(8H, m), 2.41-3.23(12H, m), 3.56-5.18              (8H, m), 6.82-7.48(11H, m)     286      1.39-1.96(8H, m), 2.03(2H, brs), 2.43-3.18(10H,              m), 3.35-5.15(4H, m), 3.99(2H, t, J=6.3Hz),              6.84-7.47(8H, m)     287      1.42-1.94(8H, m), 1.98(3H, s), 2.08(3H, s),              2.50-3.18(8H, m), 3.30-3.58(2H, m), 3.71-5.07              (4H, m), 3.97(2H, t, J=6.2Hz), 5.90-6.03(1H, m),              6.87-7.49(8H, m)     288      1.38-2.08(8H, m), 1.99(3H, s), 2.39-3.56(11H,              m), 3.58-5.11(6H, m), 6.17-6.42(1H, m), 6.82-7.48              (8H, m)     289      1.37-1.94(8H, m), 2.14-3.15(19H, m), 2.32(3H,              s), 3.58-5.07(4H, m), 3.99(2H, t, J=6.4Hz),              6.82-7.48(8H, m)     290      1.65-1.98(6H, m), 2.33-3.13(10H, m), 2.39(6H,              s), 3.88-4.99(3H, m), 4.02(2H, t, J=5.9Hz),              6.83-7.50(8H, m)     291      1.44-2.03(6H, m), 2.21(6H, s), 2.28(2H, t, J=7.2              Hz), 2.52-3.28(10H, m), 3.76-5.13(3H, m), 6.98-              7.42(8H, m)     292      1.36-1.98(10H, m), 2.12-2.39(2H, m), 2.28(6H,              s), 2.52-3.12(10H, m), 3.55-5.13(5H, m), 3.99              (2H, t, J=6.3Hz), 6.86-7.48(8H, m)     293      1.04(6H, t, J=7.1Hz), 1.32-1.95(10H, m), 2.20-              3.16(16H, m), 3.43-5.13(5H, m), 4.00(2H, t,              J=6.4Hz), 6.86-7.49(8H, m)     294      0.89(6H, t, J=7.4Hz), 1.32-1.94(16H, m), 2.26-              3.12(14H, m), 3.45-4.98(5H, m), 3.99(2H, t,              J=6.3Hz), 6.34-7.49(8H, m)     295      1.12(3H, t, J=7.1Hz), 1.38-1.96(10H, m), 2.26-              3.12(15H, m), 3.46-5.06(5H, m), 3.99(2H, t,              J=6.0Hz), 6.89(2H, d, J=8.7Hz), 6.99-7.32(4H,              m), 7.42(2H, d, J=8.7Hz)     296      1.07(6H, t, J=7.2Hz), 1.28-1.94(8H, m), 2.25-              3.17(15H, m), 3.55-5.08(7H, m), 3.96(2H, t,              J=6.5Hz), 6.42-7.33(6H, m)     297      1.04(6H, t, J=7.1Hz), 1.42-2.14(6H, m), 2.23-              3.13(14H, m), 3.56-5.02(7H, m), 6.87-7.49(8H, m)     298      1.51-2.13(10H, m), 2.52-3.40(15H, m), 3.78-5.03              (6H, m), 6.83-7.48(8H, m)     299      1.35-2.10(12H, m), 2.13-3.12(15H, m), 3.57-4.83              (6H, m), 6.82-7.53(8H, m)     300      1.44-2.12(6H, m), 2.20-3.13(15H, m), 3.15-4.86              (10H, m), 6.88-7.57(8H, m)     301      1.08(6H, t, J=7.9Hz), 1.43-1.93(8H, m), 2.40-              3.16(14H, m), 3.28-5.17(4H, m), 3.45(2H, t,              J=5.1Hz), 3.51(2H, t, J=8.0Hz), 3.99(2H, t,              J=6.4Hz), 6.84-7.48(4H, m)     302      1.48-1.93(8H, m), 2.27-3.13(10H, m), 2.45(6H,              s), 3.36-3.67(5H, m), 3.73-5.17(4H, m), 3.99(2H,              t, J=6.3Hz), 6.86-7.50(8H, m)     303      1.23(6H, t, J=7.2Hz), 1.67-1.94(2H, m) 2.06              (2H, quint, J=6.2Hz), 2.43-3.14(14H, m), 3.38-              3.62(4H, m), 3.66(2H, t, J=6.1Hz), 3.87-5.22              (4H, m), 4.08(2H, t, J=6.1Hz), 6.85-7.48(8H, m)     304      1.38-1.98(12H, m), 2.25-3.18(14H, m), 3.33-5.13              (7H, m), 6.80-7.50(8H, m)     305      1.26-1.92(8H, m), 2.15-3.13(14H, m), 2.32(3H,              s), 3.20-5.03(5H, m), 3.98(2H, t, J=6.4Hz),              6.82-7.47(13H, m)     306      1.37-1.94(8H, m), 2.28-3.23(14H, m), 2.36(3H,              s), 3.54-5.15(4H, m), 3.68(2H, t, J=4.8Hz), 4.00              (2H, t, J=6.3Hz), 6.83-7.52(8H, m)     307      1.33-1.98(8H, m), 2.28-3.18(14H, m), 3.38-5.18              (11H, m), 3.98(2H, t, J=6.2Hz), 6.78-7.48(8H, m)     308      1.35-1.98(8H, m), 2.25-3.32(18H, m), 3.38-5.10              (7H, m), 6.78-7.48(13H, m)     309      1.38-1.98(16H, m), 2.23-3.15(14H, m), 3.32-5.05              (5H, m), 4.00.(2H, t, J=6.3Hz), 6.32-7.50(8H, m)     310      1.43(6H, t, J=7.3Hz), 1.35-1.65(4H, m), 1.70-              1.98(6H, m), 2.51-3.23(4H, m), 3.77-5.23(3H, m),              3.99(2H, t, J=6.2Hz), 6.85-7.51(8H, m)     311      1.34-2.31(14H, m), 2.51-3.65(14H, m), 3.70-5.14              (3H, m), 3.98(2H, t, J=6.2Hz), 6.83-7.50(8H, m)     312      1.46-2.06(12H, m), 2.16-3.13(14H, m), 3.33-5.07              (5H, m), 4.00(2H, t, J=6.0Hz), 6.83-7.48(8H, m)     313      1.13(3H, t, J=7.2Hz), 1.38-2.02(9H, m), 2.37-              3.13(12H, m), 3.53-5.12(3H, m), 3.99(2H, t,              J=6.3Hz), 6.82-7.52(8H, m)     314      1.11(6H, dd, J=6.3, 1.0Hz), 1.38-1.95(8H, m),              2.35-3.12(13H, m), 3.46-5.09(4H, m), 3.99(2H, t,              J=6.3Hz), 6.32-7.49(8H, m)     315      1.02(3H, t, J=7.1Hz), 1.28-2.03(14H, m), 2.21-              3.12(14H, m), 3.28-5.12(8H, m), 3.99(2H, t,              J=6.4Hz), 6.82-7.48(8H, m)     316      1.38-1.96(8H, m), 2.28-3.13(17H, m), 3.62-5.08              (5H, m), 3.99(2H, t, J=6.3Hz), 6.82-7.48(13H, m)     317      1.37-2.00(12H, m), 2.18-3.30(15H, m), 3.40-5.16              (4H, m), 3.47(1H, dd, J=11.1, 4.1Hz), 3.62(1H,              dd, J=11.1, 4.1Hz), 3.99(2H, t, J=6.4Hz), 6.82-              7.48(8H, m)     318      1.35-1.95(8H, m), 2.18-3.13(10H, m), 2.24(3H,              s), 3.46(1H, d, J=13.0Hz), 3.69(1H, d, J=13.0              Hz), 3.55-5.14(4H, m), 3.99(2H, t, J=6.3Hz),              6.82-7.48(13H, m)     319      1.65-2.08(6H, m), 2.46-3.49(10H, m), 3.78-5.08              (5H, m), 6.81(2H, d, J=8.7Hz), 6.95-7.75(10H,              m), 11.40(1H, brs)     320      1.30-1.99(10H, m), 2.45-3.20(8H, m), 3.74-5.20              (5H, m), 3.98(2H, t, J=6.4Hz), 4.06(2H, t, J=6.6              Hz), 6.90(2H, d, J=8.7Hz), 6.93-7.57(6H, m)     321      1.68-2.32(6H, m), 2.49-3.64(10H, m), 3.77-5.10              (5H, m), 6.80(2H, d, J=9.1Hz), 6.96-7.91(10H,              m), 12.03(1H, s)     322      1.55-1.97(2H, m), 2.07-2.32(2H, m), 2.55-5.17              (7H, m), 3.92(2H, t, J=6.8Hz), 4.06(2H, t, J=6              Hz), 6.65(1H, d, J=9.4Hz), 6.82(2H, d, J=8.7              Hz), 7.10-8.05(11H, m),     323      1.61-2.08(6H, m), 2.65-3.34(4H, m), 2.93(2H, t,              J=6.8Hz), 3.88-5.20(3H, m), 4.09(2H, t, J=6Hz),              6.65(1H, d, J=9.4Hz), 6.93(2H, d, J=8.8Hz),              7.11-7.77(7H, m)     324      1.62-2.09(4H, m), 1.93(3H, s), 2.60-3.49(6H, m),              3.85-5.15(3H, m), 4.00(2H, t, J=5.9Hz), 6.00              (1H, brs), 6.59(1H, d, J=9.4Hz), 6.85(2H, d,              J=8.7Hz), 7.08-7.66(7H, m)     325      1.30-2.15(8H, m), 2.32-3.20(8H, m), 3.53-4.05              (6H, m), 4.20-4.78(1H, m), 4.80-5.15(3H, m),              5.70-5.93(1H, m), 6.38-6.88(4H, m), 7.10-7.35              (1H, m)     326      1.28-1.96(8H, m), 2.30-3.21(11H, m), 3.56-4.10              (6H, m), 4.12-4.78(1H, m), 4.83-5.10(1H, m),              6.40-6.85(4H, m), 7.12-7.32(1H, m)     327      1.41(3H, t, J=6.9Hz), 1.52-1.90(2H, m), 2.30              (3H, s), 2.38-3.27(8H, m), 3.55-3.93(4H, m), 4.04              (2H, q, J=6.9Hz), 4.20-4.68(1H, m), 4.80-5.08              (1H, m), 6.35-6.64(2H, m), 6.78-7.37(4H, m)     328      1.64-1.86(3H, m), 2.30(3H, s), 2.40-2.90(8H, m),              3.12-3.31(2H, m), 4.20-4.40(1H, m), 6.82-7.20              (3H, m)     ______________________________________

Example 588

To 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-ethoxycarbonyl-3,4-dihydrocarbostyril (0.48 g) are added sodium hydroxide (0.2 g), water (4 ml) and ethanol (10 ml) and the mixture is stirred at room temperature for 30 minutes. Water is added to the reaction mixture and the mixture is extracted with ethyl acetate. The aqueous layer is neutiralized with acetic acid and extracted with dichloromethane. The extract is concentrated to give 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-carboxy-3,4-dihydrocarbostyril (0.38 g) as white amorphous form.

NMR (CDCl₃) δ ppm: 1.42 (3H, t, J=7.0 Hz), 1.58-2.05 (2H, m), 2.35-3.47 (7H, m), 3.55-3.95 (4H, m), 4.04 (2H, q, J=7 Hz), 4.38 (1H, brs), 4.94 (1H, brs), 6.37-6.56 (2H, m), 7.00-7.40 (5H, m)

Example 589

To 1-[1-(2-methoxy-4-ethoxybenzoyl)4-piperidinyl]-3-ethoxycarbonyl-3,4-dihydrocarbstyril (1.1 g) are added hydrazine monohydrate (1.1 g) and ethanol (15 ml) and the mixture is refluxed with heating for 7 hours. The reaction mixture is concentrated and the residue is purified by silica gel column chromatography (solvent: dichloromethane→dichloromethane:methanol=20:1) to give 1-[1-(2-methoxy-4-ethoxybenzoyl)4-piperidinyl]-3-hydrazinocarbonyl-3,4-dihydrocarbostyril (0.9 g) as white amorphous form.

NMR (CDCl₃) δ ppm: 1.42 (3H, t, J=7.0 Hz), 1.52-1.95 (2H, m), 2.30-3.93 (13H, m), 4.04 (2H, q, J=7 Hz), 4.15-5.06 (3H, m), 6.40-6.62 (2H, m), 6.97-7.50 (5H, m)

Example 590

To 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-hydrazinocarbonyl-3,4-dihydrocarbostyril (1.4 g) are added dichloromethane (14 ml), 10% hydrochloric acid (5.5 ml) and water (14 ml). To the mixture is added dropwise a solution of sodium nitrite (0.25 g) in water (3 ml) at a temperature below 5° C. The mixture is stirred at 5° C. for 15 minutes. The dichloromethane layer is separated, dried and concentrated. To the resulting residue are added benzyl alcohol (0.5 g) and toluene (7 ml) and the mixture is refluxed with heating for 2 hours. After cocentration, the resulting residue is purified by silica gel column chromatography (solvent: dichloromethane) to give 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-benzyloxycarbonylamino-3,4-dihydrocarbostyril (0.9 g) as white amorphous form.

NMR (CDCl₃) δ ppm: 1.40 (3H, t, J=7.0 Hz), 1.55-2.00 (2H, m), 2.30-5.05 (15H, m), 5.30 (2H, s), 5.95 (1H, brs), 6.50-6.60 (2H, m), 7.02-7.42 (10H, m)

Example 591

To 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-benzyloxycarbonylamino-3,4-dihydrocarbostyril (0.8 g) are added ethanol (20 ml) and 10% palladium-carbon (0.15 g) and the mixture is subjected to catalytic reduction at room temperature for 4 hours. After the catalyst is removed by filtration, the resulting filtrate is concentrated. To the residue are added ethanol (5 ml) and conc. hydrochloric acid (0.2 ml) and the mixture is concentrated again. Diethyl ether is added to the residue and the precipitated crystal is collected by filtration and recrystallized from ethanol to give 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-amino-3,4-dihydrocarbostyril.hydrochloride (0.52 g) as white powder, m.p.: 257°-260° C.

Example 592

To 1-{1-[4-(5-carboxypentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2.00 g) are added 3,4-diaminopyridine (0.47 g), phosphorus pentoxide (1.00 g) and methanesulfonic acid (7.0 ml) and the mixture is stirred with heating at 100°-120° C. for 3 hours. After cooling, the reaction solution is poured into ice-water (30 ml) and the mixture is adjusted to around pH 11 with aqueous sodium hydroxide solution and extracted with dichloromethane. The extract is dried with magnesium sulfate and the solvent is distilled off. The resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=20:1→9:1) to give 1-{1-[4-(5-(imidazo[4,5-c]pyridine-2-yl)carboxypentyloxy)benzoyl]-4-piperidinyl]-3,4-dihydrocarbostyril (1.32 g) as white amorphous form.

NMR (CDCl₃) δ ppm: 1.42-1.64 (2H, m), 1.64-2.06 (6H, m), 2.57 (2H, t, J=6.1 Hz), 2.64-3.24 (8H, m), 3.67-5.15 (2H, m), 3.92 (2H, t, J=6.1 Hz), 4.34 (1H, m), 6.84 (2H, d, J=8.7 Hz), 7.00-7.36 (5H, m), 7.40 (2H, d, J=8.7 Hz), 8.28 (1H, d, J=5.6 Hz), 8.80 (1H, s)

Example 593

To methyl 2-methyl-5-[(1-benzyl-4-piperidinyl)amino]cinnamate (1.0 g) are added acetic acid (10 ml), conc. hydrochloric acid (3 ml), water (3 ml) and 10% palladium-carbon (0.2 g) and the mixture is subjected to catalytic reduction at 90° C. for 2 hours under atmospheric pressure. After cooling, the catalyst is removed by filtration and the filtrate is concentrated. Water is added to the resulting residue and the mixture is basified with potassium carbonate and then extracted with dichloromethane. The solvent is concentrated to give 5-methyl-1-(4-piperidinyl)-3,4-dihydrocarbostyril (0.6 g) as colorless amorphous form.

NMR (CDCl₃) δ ppm: 1.64-1.86 (3H, m), 2.30 (3H, s), 2.40-2.90 (8H, m), 3.12-3.31 (2H, m), 4.20-4.40 (1H, m), 6.82-7.20 (3H, m)

Using the suitable starting materials, the compounds of the above Examples 1-9, 11-164, 169-383C, 435-474A and 482-577A are obtained in the same manners as Example 593.

Using the suitable starting materials, the following compounds are obtained in the same manners as in Examples 1, 384 and 593.

                                      TABLE 9     __________________________________________________________________________      ##STR608##     __________________________________________________________________________     Example 594     Structure      ##STR609##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 491)     Form: Free     Example 595     Structure      ##STR610##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 492)     Form: Free     Example 596     Structure      ##STR611##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 329)     Form: Free     Example 597     Structure      ##STR612##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 330)     Form: Free     Example 598     Structure      ##STR613##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 331)     Form: Free     Example 599     Structure      ##STR614##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 332)     Form: Free     Example 600     Structure      ##STR615##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 333)     Form: Free     Example 601     Structure      ##STR616##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 334)     Form: Free     Example 602     Structure      ##STR617##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 335)     Form: Free     Example 603     Structure      ##STR618##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 336)     Form: Free     Example 604     Structure      ##STR619##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 337)     Form: Free     Example 605     Structure      ##STR620##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 338)     Form: Free     Example 606     Structure      ##STR621##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 339)     Form: Free     Example 607     Structure      ##STR622##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 340)     Form: Free     Example 608     Structure      ##STR623##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 341)     Form: Free     Example 609     Structure      ##STR624##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 342)     Form: Free     Example 610     Structure      ##STR625##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 343)     Form: Free     Example 611     Structure      ##STR626##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 344)     Form: Free     Example 612     Structure      ##STR627##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 345)     Form: Free     Example 613     Structure      ##STR628##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 346)     Form: Free     Example 614     Structure      ##STR629##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 347)     Form: Free     Example 615     Structure      ##STR630##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in.the     carbostyril ring: Single bond     NMR analysis: 348)     Form: Free     Example 616     Structure      ##STR631##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 349)     Form: Free     Example 617     Structure      ##STR632##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 350)     Form: Free     Example 618     Structure      ##STR633##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 351)     Form: Free     Example 619     Structure      ##STR634##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 352)     Form: Free     Example 620     Structure      ##STR635##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 353)     Form: Free     Example 621     Structure      ##STR636##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 354)     Form: Free     Example 622     Structure      ##STR637##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 355)     Form: Free     Example 623     Structure      ##STR638##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 356)     Form: Free     Example 624     Structure      ##STR639##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 357)     Form: Free     Example 625     Structure      ##STR640##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 358)     Form: Free     Example 626     Structure      ##STR641##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 359)     Form: Free     Example 627     Structure      ##STR642##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 360)     Form: Free     Example 628     Structure      ##STR643##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 361)     Form: Free     Example 629     Structure      ##STR644##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 362)     Form: Free     Example 630     Structure      ##STR645##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 363)     Form: Free     Example 631     Structure      ##STR646##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 364)     Form: Free     Example 632     Structure      ##STR647##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 365)     Form: Free     Example 633     Structure      ##STR648##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 366)     Form: Free     Example 634     Structure      ##STR649##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 367)     Form: Free     Example 635     Structure      ##STR650##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 368)     Form: Free     Example 636     Structure      ##STR651##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 369)     Form: Free     Example 637     Structure      ##STR652##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 370)     Form: Free     Example 638     Structure      ##STR653##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 371)     Form: Free     Example 639     Structure      ##STR654##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 372)     Form: Free     Example 640     Structure      ##STR655##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 373)     Form: Free     Example 641     Structure      ##STR656##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions-in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 374)     Form: Free     Example 642     Structure      ##STR657##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 375)     Form: Free     Example 643     Structure      ##STR658##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 376)     Form: Free     Example 644     Structure      ##STR659##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 377)     Form: Free     Example 645     Structure      ##STR660##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 378)     Form: Free     Example 646     Structure      ##STR661##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 379)     Form: Free     Example 647     Structure      ##STR662##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 380)     Form: Free     Example 648     Structure      ##STR663##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 381)     Form: Free     Example 649     Structure      ##STR664##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 382)     Form: Free     Example 650     Structure      ##STR665##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 383)     Form: Free     Example 651     Structure      ##STR666##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 384)     Form: Free     Example 652     Structure      ##STR667##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 385)     Form: Free     Example 653     Structure      ##STR668##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 386)     Form: Free     Example 654     Structure      ##STR669##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 387)     Form: Free     Example 655     Structure      ##STR670##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 388)     Form: Free     Example 656     Structure      ##STR671##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 389)     Form: Free     Example 657     Structure      ##STR672##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 390)     Form: Free     Example 658     Structure      ##STR673##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 391)     Form: Free     Example 659     Structure      ##STR674##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 152-155° C.     Form: Oxalate     Example 660     Structure      ##STR675##     R.sup.1 : H,   q: 1     Bond between 3- and 4- positions in the     carbostyril ring: Single bond     NMR analysis: 392)     Form: Free     Example 661     Structure      ##STR676##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 393)     Form: Free     Example 662     Structure      ##STR677##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 394)     Form: Free     Example 663     Structure      ##STR678##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 395)     Form: Free     Example 664     Structure      ##STR679##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 396)     Form: Free     Example 665     Structure      ##STR680##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 397)     Form: Free     Example 666     Structure      ##STR681##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 398)     Form: Free     Example 667     Structure      ##STR682##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 399)     Form: Free     Example 668     Structure      ##STR683##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 400)     Form: Free     Example 669     Structure      ##STR684##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/water     Melting point: 216-217° C.   Form: Dioxalate     Example 670     Structure      ##STR685##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/water     Melting point: 216-217° C.   Form: Dioxalate     Example 671     Structure      ##STR686##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Ethanol/water     Melting point: 215-218° C.   Form: Dioxalate     Example 672     Structure      ##STR687##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorles needles     Recrystallization solvent: Ethanol/water     Melting point: 195-196° C.   Form: Dioxalate     Example 673     Structure      ##STR688##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 401)     Form: Free     Example 674     Structure      ##STR689##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 402)     Ms (m/z): 562   Form: Free     Example 675     Structure      ##STR690##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 403)     Form: Free     Example 676     Structure      ##STR691##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 404)     Form: Free     Example 677     Structure      ##STR692##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 405)     Form: Free     Example 678     Structure      ##STR693##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 406)     Form: Free     Example 679     Structure      ##STR694##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 407)     Form: Free     Example 680     Structure      ##STR695##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 408)     Form: Free     Example 681     Structure      ##STR696##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 409)     Form: Free     Example 682     Structure      ##STR697##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 410)     Form: Hydrochloride     Example 683     Structure      ##STR698##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 411)     Form: Free     Example 684     Structure      ##STR699##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Light yellow amorphous form     NMR analysis: 412)     Form: Hydrochloride     Example 685     Structure      ##STR700##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 413)     Form: Free     Example 686     Structure      ##STR701##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 414)     Form: Free     Example 687     Structure      ##STR702##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 415)     Form: Free     Example 688     Structure      ##STR703##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 416)     Form: Free     Example 689     Structure      ##STR704##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 417)     Form: Free     Example 690     Structure      ##STR705##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 418)     FAB-MS (Pos.) (m/z): 551   Form: I.sup.⊖     Example 691     Structure      ##STR706##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 419)     Form: Free     Example 692     Structure      ##STR707##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 420)     Form: Free     Example 693     Structure      ##STR708##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 421)     Form: Free     Example 694     Structure      ##STR709##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 422)     Form: Free     Example 695     Structure      ##STR710##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 423)     Form: Free     Example 696     Structure      ##STR711##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 424)     Form: Free     Example 697     Structure      ##STR712##     R.sup.1 : H,   q: =1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 425)     Form: Free     Example 698     Structure      ##STR713##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 426)     Form: Free     Example 699     Structure      ##STR714##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 427)     Form: Br.sup.⊖     Example 700     Structure      ##STR715##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 428)     Form: Free     Example 701     Structure      ##STR716##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 429)     Form: tree     Example 702     Structure      ##STR717##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 430)     Form: Free     Example 703     Structure      ##STR718##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 431)     Form: Free     Example 704     Structure      ##STR719##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 432)     Form: Free     Example 705     Structure      ##STR720##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 433)     Form: Free     Example 706     Structure      ##STR721##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 434)     Form: Free     Example 707     Structure      ##STR722##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 435)     Form: Free     Example 708     Structure      ##STR723##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 436)     Form: Free     Example 709     Structure      ##STR724##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 437)     Form: Free     Example 710     Structure      ##STR725##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 438)     Form: Free     Example 711     Structure      ##STR726##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 439)     Form: Free     Example 712     Structure      ##STR727##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 440)     Form: Free     Example 713     Structure      ##STR728##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 441)     Form: Free     Example 714     Structure      ##STR729##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 442)     Form: Free     Example 715     Structure      ##STR730##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 443)     Form: Free     Example 716     Structure      ##STR731##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 444)   Form: Free     Example 717     Structure      ##STR732##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 445)   Form: Free     Example 718     Structure      ##STR733##     R.sup.1 : OH (5-position),  q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent:. Methanol/diethyl ether     Melting point: 274° C. (decomposed)   Form: Hydrochloride     Example 719     Structure      ##STR734##     R.sup.1 : OC.sub.2 H.sub.5 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Recrystallization solvent: Methanol/diethyl ether     Melting point: 250° C. (decomposed)     Form: Hydrochloride     Example 720     Structure      ##STR735##     R.sup.1 : OH (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 446)   Form: Free     Example 721     Structure      ##STR736##     R.sup.1 : OH (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 447)   Form: Free     Example 722     Structure      ##STR737##     R.sup.1 : OCH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 448)   Form: Free     Example 723     Structure      ##STR738##     R.sup.1 : OC.sub.2 H.sub.5 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 449)   Form: Free     Example 724     Structure      ##STR739##     R.sup.1 : OC.sub.2 H.sub.5 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 450)   Form: Free     Example 725     Structure      ##STR740##     R.sup.1 : OCOCH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 451)   Form: Free     Example 726     Structure      ##STR741##     R.sup.1 : OCH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 452)   Form: Free     Example 727     Structure      ##STR742##     R.sup.1 : OCOCH.sub.3,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 453)   Form: Free     Example 728     Structure      ##STR743##     R.sup.1 : CH.sub.3 (5-, 7-positions),   q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Melting point: 278-282° C.     Form: Hydrochloride     Example 729     Structure      ##STR744##     R.sup.1 : CH.sub.3 (5-, 7-positions),   q: 2     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: White powders     Melting point: 165-167° C.     Form: Free     Example 730     Structure      ##STR745##     R.sup.1 : F (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 454)     Form: Free     Example 731     Structure      ##STR746##     R.sup.1 : F (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 455)     Form: Free     Example 732     Structure      ##STR747##     R.sup.1 : F (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 456)     Form: Free     Example 733     Structure      ##STR748##     R.sup.1 : CH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 457)     Form: Free     Example 734     Structure      ##STR749##     R.sup.1 : CH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 458)     Form: Free     Example 735     Structure      ##STR750##     R.sup.1 : CH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 459)     Form: Free     Example 736     Structure      ##STR751##     R.sup.1 : CH.sub.3 (5-position),   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 460)     Form: Free     Example 737     Structure      ##STR752##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis:: 461)     Form: Free     Example 738     Structure      ##STR753##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 462)     Form: Free     Example 739     Structure      ##STR754##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 463)     Form: Free     Example 740     Structure      ##STR755##     R.sup.1 : H,   q: 1     Bond between 3- and 4- positions in the     carbostyril ring: Single bond     NMR analysis: 464)     Form: Free     Example 741     Structure      ##STR756##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 465)     Form: Free     Example 742     Structure      ##STR757##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 466)     Form: Free     Example 743     Structure      ##STR758##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 467)     Form: Free     Example 744     Structure      ##STR759##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 468)     Form: Free     Example 745     Structure      ##STR760##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 469)     Form: Free     Example 746     Structure      ##STR761##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 470)     Form: Free     Example 747     Structure      ##STR762##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 471)     Form: Free     Example 748     Structure      ##STR763##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 472)     Form: Free     Example 749     Structure      ##STR764##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 473)     Form: Free     Example 750     Structure      ##STR765##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 474)     Form: Free     Example 751     Structure      ##STR766##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 475)     Form: Free     Example 752     Structure      ##STR767##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 476)     Form: Free     Example 753     Structure      ##STR768##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 477)     Form: Free     Example 754     Structure      ##STR769##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 478)     Form: Free     Example 755     Structure      ##STR770##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 479)     Form: Free     Example 756     Structure      ##STR771##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 480)     Form: Free     Example 757     Structure      ##STR772##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 481)     Form: Free     Example 758     Structure      ##STR773##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 482)   Form: Free     Example 759     Structure      ##STR774##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 483)    Form: Free     Example 760     Structure      ##STR775##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless needles     Recrystallization solvent: Ethanol/diethyl ether     Melting point: 155-157° C.    Form: Free     Example 761     Structure      ##STR776##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 484)   Form: Free     Example 762     Structure      ##STR777##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 485)    Form: Free     Example 763     Structure      ##STR778##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysts: 486)    Form: Dihydrochloride     Example 764     Structure      ##STR779##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 487)    Form: Free     Example 765     Structure      ##STR780##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 488)    Form: Free     Example 766     Structure      ##STR781##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 489)    Form: Free     Example 767     Structure      ##STR782##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     Crystalline form: Colorless amorphous form     NMR analysis: 490)     Form: Free     Example 768     Structure      ##STR783##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 493)     Form: Free     Example 769     Structure      ##STR784##     R.sup.1 : H,   q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 494)     Form: Free     __________________________________________________________________________

Example 770

1-{1-[4-(4-Oxiranylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.6 g) is dissolved in a mixture of dioxane (30 ml) and water (10 ml). Thereto is added conc. sulfuric acid (0.1 ml) and the mixture is stirred at room temperature overnight. The mixture is neutralized with sodium hydrogen carbonate and then extracted with chloroform. The extract is dried with magnesium sulfate and the solvent is evaporated off. The resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=50:1) to give 1-{1-[4-(5,6-dihydroxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.6 g).

NMR (CDCl₃) δ ppm: 1.35-1.93 (8H, m), 2.15-3.15 (10H, m), 3.32-3.78 (3H, m), 3.83-5.22 (3H, m), 3.97 (2H, t, J=6.3 Hz), 6.79-7.48 (8H, m)

Example 771

Using the suitable starting materials, the compounds of the above Examples 718, 719, 728 and 730 are obtained in the same manners as Example 386.

Example 772

Using the suitable starting materials, the compounds of the above Examples 594-717, 720-727, 729, 731-769 are obtained in the same manners as in Examples 390-393.

Example 773

Using the suitable starting materials, the compounds of the above Examples 594-717, 720-727, 729, 731-769 are obtained in the same manners as in Examples 398 and 399.

Example 774

Using the suitable starting materials, the compounds of the above Examples 596-648, 650-651, 653, 700, 712, 714, 716, 717, 720, 723, 726, 727, 733, 747, 757, and 760 are obtained in the same manners as in Examples 403-405.

Example 775

Using the suitable starting materials, the compounds of the above Examples 600, 604, 609, 610, 616, 618, 620, 623, 625, 627, 628, 630, 631, 633, 634, 637-639, 646, 649, 651, 652-655, 658-660, 662, 663, 666, 668-671, 673, 677, 685-687, 689-691, 698, 699, 715, 735-738, 742-744, 746-752, 755, 756, 762-764, 768-769 are obtained in the same manners as in Examples 407-409.

Example 776

Using the suitable starting materials, the compounds of the above Examples 695, 696, 697, 706, 709-712, 715, 751, 766 and 767 are obtained in the same manners as in Example 416.

Example 777

Using the suitable starting materials, the compounds of the above Examples 657-661, 663, 664, 674, 676, 677 and 692 are obtained in the same manners as in Example 421.

Example 778

Using the suitable starting materials, the compounds of the above Examples 596-603, 605, 606, 611-616, 618-623, 625-640, 642, 643, 645-656, 662, 665-673, 675, 678-689, 691, 693, 694, 698, 700-705, 707, 708, 713, 714, 716, 717, 720, 723, 726, 727, 733, 735-750, 753-757, 760-763, 768 and 769 are obtained in the same manners as in Example 426.

                  TABLE 10     ______________________________________     No.     NMR (CDCl.sub.3) δ value     ______________________________________     329     1.64-2.44(8H, m), 2.50-3.20(8H, m), 3.25-3.70             (4H, m), 3.80-5.00(2H, brs), 3.99(2H, m), 4.33             (2H, m), 5.07(1H, d, J=12.5Hz), 5.19(1H, d,             J=12.5Hz), 6.38(1H, brs), 6.89(2H, d, J=8.4Hz),             6.99-7.28(4H, m), 7.33(5H, m), 7.42(2H, d, J=8.4Hz)     330     1.25-2.20(6H, m), 1.80(2H, m), 1.95(2H, m),             2.52-3.04(8H, m), 3.12(2H, m), 3.41(2H, q, J=5.4             Hz), 3.80-4.90(2H, brs), 3.98(2H, t, J=5.4Hz),             4.10(1H, m), 4.35(1H, m), 5.29(4H, s), 5.31(1H,             brs), 5.70(1H, brs), 6.72(1H, brs), 6.87(2H, d,             J=8.6Hz), 6.98-7.27(4H, m), 7.30(10H, s), 7.39             (2H, d, J=8.6Hz)     331     1.84(2H, m), 2.40-3.15(10H, m), 3.23-3.50(2H,             m), 3.56(2H, t, J=6.1Hz), 3.70-5.15(2H, brs),             3.94(2H, t, J=5.6Hz), 4.35(2H, m), 6.61(2H, d,             J=8.0Hz), 6.84(2H, d, J=8.6Hz), 6.92(2H, d,             J=8.0Hz), 6.99-7.29(4H, m), 7.40(2H, d, J=8.6             Hz), 7.50(1H, brs)     332     1.65-2.50(8H, m), 2.50-3.10(10H, m), 3.45(2H, q,             J=6.4Hz), 3.60-5.10(2H, brs), 3.81(1H, dd,             J=9.0, 5.3Hz), 4.06(2H, t, J=5.9Hz), 4.38(1H,             m), 6.92(2H, d, J=8.7Hz), 6.99-7.29(4H, m), 7.43             (2H, d, J=8.7Hz), 8.00(1H, brs)     333     1.70-1.93(2H, m), 2.04(2H, quint, J=6.2Hz), 2.30             (6H, s), 2.53-3.20(8H, m), 2.96(2H, s), 3.50(2H,             q, J=6.2Hz), 3.80-5.10(2H, brs), 4.08(2H, t,             J=6.2Hz), 4.37(1H, m), 6.92(2H, d, J=8.7Hz),             6.99-7.29(4H, m), 7.44(2H, d, J=8.7Hz), 7.53             (1H, brs)     334     1.60-1.89(2H, m), 1.97(2H, quint, J=6.0Hz),             2.53-3.20(8H, m), 3.44(2H, q, J=6.0Hz), 3.64             (1H, dd, J=11.2, 5.2Hz), 3.80-5.10(2H, brs), 4.00             (2H, t, J=6.0Hz), 4.12(1H, dd, J=11.2, 5.2Hz),             4.17(1H, m), 4.35(1H, m), 5.10(2H, s), 5.97(1H,             d, J=6.0Hz), 6.89(2H, d, J=8.7Hz), 6.99-7.30             (4H, m), 7.33(5H, s), 7.39(2H, d, J=8.7Hz)     335     1.37(3H, d, J=7.0Hz), 1.64-1.90(2H, m), 1.97             (2H, m), 2.53-3.20(8H, m), 3.43(2H, q, J=6.2Hz),             3.65-5.00(2H, brs), 4.00(2H, t, J=5.8Hz), 4.21             (1H, quint, J=7.0Hz), 4.37(1H, m), 5.05(1H, d,             J=12.1Hz), 5.18(1H, d, J=12.1Hz), 5.55(1H, d,             J=7.0Hz), 6.70(1H, brs), 6.88(2H, d, J=8.7Hz),             6.99-7.36(4H, m), 7.33(5H, s), 7.40(2H, d, J=8.7Hz)     336     1.33(3H, d, J=6.9Hz), 1.63-1.95(2H, m), 2.03             (2H, quint, J=6.0Hz), 2.53-3.20(8H, m), 3.41-3.55             (3H, m), 3.80-5.20(2H, brs), 4.06(2H, t, J=6.0             Hz), 4.37(1H, m), 6.93(2H, d, J=8.6Hz), 6.99-             7.89(4H, m), 7.43(2H, d, J=8.6Hz), 7.68(1H, t,             J=6.0Hz)     337     1.42-1.62(2H, m), 1.62-1.90(6H, m), 2.31-2.44             (6H, m), 2.54-3.10(8H, m), 3.46(2H, m), 3.51(2H,             s), 3.63(2H, m), 3.83-5.15(2H, brs), 3.98(2H, t,             J=6.4Hz), 4.39(1H, m), 6.89(2H, d, J=8.7Hz),             6.99-7.33(4H, m), 7.31(5H, s), 7.42(2H, d, J=8.7Hz)     338     0.82(3H, d, J=6.9Hz), 0.99(3H, d, J=6.9Hz),             1.64-1.90(2H, m), 2.04(2H, m), 2.10-2.41(1H, m),             2.54-3.08(8H, m), 3.24(1H, d, J=3.8Hz), 3.48             (2H, q, J=6.5Hz), 3.67-5.50(2H, brs), 4.06(2H,             t, J=5.9Hz), 4.38(1H, m), 6.92(2H, d, J=8.7Hz),             6.99-7.28(4H, m), 7.43(2H, d, J=8.7Hz), 7.67             (1H, brs)     339     0.82(3H, d, J=6.9Hz), 0.99(3H, d, J=6.9Hz),             1.68-1.93(2H, m), 2.03(2H, quint, J=6.1Hz), 2.33             (1H, m), 2.54-3.17(8H, m), 3.25(1H, d, J=3.7Hz),             3.49(2H, q, J=6.1Hz), 3.80-5.20(2H, brs), 4.07             (2H, t, J=6.1Hz), 4.39(1H, m), 6.92(2H, d, J=8.7             Hz), 7.03-7.30(4H, m), 7.43(2H, d, J=8.7Hz),             7.64(1H, brs)     340     1.41-1.60(2H, m), 1.61-1.98(6H, m), 2.35(2H, t,             J=7.4Hz), 2.54-3.10(12H, m), 3.44(2H, t, J=4.9             Hz), 3.59(2H, t, J=4.9Hz), 3.80-5.20(2H, brs),             3.99(2H, t, J=6.3Hz), 4.39(1H, m), 6.89(2H, d,             J=8.6Hz), 6.99-7.28(4H, m), 7.42(2H, d, J=8.6Hz)     341     1.40-1.65(2H, m), 1.65-2.00(6H, m), 1.76(3H, s),             2.39(2H, t, J=7.4Hz), 2.54-3.20(8H, m), 3.49             (4H, m), 3.61(4H, m), 3.85-5.20(2H, brs), 4.00             (2H, t, J=6.3Hz), 4.39(1H, m), 6.89(2H, d, J=8.7             Hz), 6.99-7.25(4H, m), 7.42(2H, d, J=8.7Hz)     342     1.40-1.65(2H, m), 1.65-2.02(6H, m), 2.37(2H, t,             J=7.3Hz), 2.54-3.30(12H, m), 2.81(3H, s), 3.46-             4.10(4H, m), 4.00(2H, t, J=6.2Hz), 4.10-5.20             (2H, brs), 4.37(1H, m), 6.90(2H, d, J=8.7Hz),             7.00-7.26(4H, m), 7.42(2H, d, J=8.7Hz)     343     1.42-1.63(2H, m), 1.64-2.00(6H, m), 2.32-2.52             (6H, m), 2.54-3.10(8H, m), 3.01(2H, d, J=6.6Hz),             3.48(2H, m), 3.64(2H, m), 3.80-5.10(2H, brs),             3.99(2H, t, J=6.3Hz), 4.40(1H, m), 5.18(1H, d,             J=10.3Hz), 5.20(1H, d, J=16.8Hz), 5.85(1H, ddt,             J=16.8, 10.3, 6.6Hz), 6.89(2H, d, J=8.7Hz),             6.99-7.26(4H, m), 7.42(2H, d, J=8.7Hz)     344     1.60-1.90(2H, m), 1.81(2H, quint, J=7.0Hz), 1.98             (2H, quint, J=6.2Hz), 2.25(2H, t, J=7.0Hz),             2.52-3.17(10H, m), 3.39(2H, q, J=6.2Hz), 3.65-             5.15(2H, br), 3.90(2H, brs), 4.03(2H, t, J=6.2             Hz), 4.33(1H, m), 6.91(2H, d, J=8.5Hz), 6.98-             7.28(5H, m), 7.40(2H, d, J=8.5Hz)     345     1.70-1.93(2H, m), 1.81(2H, quint, J=6.6Hz), 1.98             (2H, quint, J=6.1Hz), 2.22(2H, t, J=6.6Hz),             2.46-3.10(8H, m), 3.21(2H, q, J=6.6Hz), 3.40             (2H, q, J=6.1Hz), 3.80-5.10(2H, brs), 4.01(2H,             t, J=6.1Hz), 4.34(1H, m), 5.07(2H, s), 5.73(1H,             brs), 6.89(2H, d, J=8.7Hz), 6.91(1H, brs), 6.99-             7.25(4H, m), 7.32(5H, s), 7.40(2H, d, J=8.7Hz)     346     1.52(4H, m), 1.66-1.97(6H, m), 2.20(2H, t, J=6.8             Hz), 2.53-3.05(8H, m), 3.10-3.32(4H, m), 3.70-             5.10(2H, br), 3.96(2H, t, J=6.3Hz), 4.37(1H,             m), 5.08(2H, s), 5.31(1H, brs), 6.30(1H, brs),             6.88(2H, d, J=8.7Hz), 6.99-7.27(4H, m), 7.33             (5H, s), 7.41(2H, d, J=8.7Hz)     347     1.41-1.71(4H, m), 1.71-1.90(4H, m), 2.54-3.20             (8H, m), 3.34(2H, q, J=6.5Hz), 3.60-5.15(2H,             brs), 3.99(2H, t, J=6.2Hz), 4.04(2H, s) 4.38             (1H, m), 6.72(1H, brs), 6.90(2H, d, J=8.5Hz),             6.99-7.28(4H, m), 7.43(2H, d, J=8.7Hz)     348     1.32-1.67(4H, m), 1.67-2.00(6H, m), 2.25(2H, t,             J=7.3Hz), 2.53-3.10(10H, m), 3.24(2H, q, J=6.2             Hz), 3.70-5.20(2H, brs), 3.97(2H, t, J=6.2Hz),             4.36(1H, m), 6.54(1H, m), 6.89(2H, d, J=8.7Hz),             6.99-7.23(4H, m), 7.41(2H, d, J=8.7Hz)     349     1.25-1.72(4H, m), 1.73-1.94(4H, m), 2.29(6H, s),             2.54-3.10(8H, m), 2.94(2H, s), 3.31(2H, q, J=6.3             Hz), 3.74-5.10(2H, br), 3.99(2H, t, J=6.3Hz),             4.39(1H, m), 6.89(2H, d, J=8.7Hz), 6.99-7.28             (5H, m), 7.43(2H, d, J=8.7Hz)     350     1.26(3H, t, J=7.1Hz), 1.42-2.05(12H, m), 2.37             (2H, t, J=7.4Hz), 2.44-3.25(11H, m), 3.50-5.10             (2H, brs), 3.73-3.94(1H, m), 3.99(2H, t, J=6.3             Hz), 4.15(2H, q, J=7.1Hz), 4.23-4.53(2H, m),             6.90(2H, d, J=8.7Hz), 6.99-7.29(4H, m), 7.42             (2H, d, J=8.7Hz)     351     1.02(6H, t, J=7.1Hz), 1.39-1.71(4H, m), 1.71-             2.05(4H, m), 2.38-3.14(8H, m), 2.55(4H, q, J=7.1             Hz), 3.01(2H, s), 3.30(2H, q, J=6.3Hz), 3.70-             5.15(2H, brs), 3.98(2H, t, J=6.3Hz), 4.39(1H,             m), 6.89(2H, d, J=8.7Hz), 6.99-7.27(4H, m), 7.43             (2H, d, J=8.7Hz), 7.45(1H, brs)     352     1.37-1.68(4H, m), 1.68-1.90(6H, m), 1.96(3H, s),             2.16(2H, t, J=6.7Hz), 2.54-3.15(8H, m), 3.15-             3.33(4H, m), 3.75-5.20(2H, brs), 3.98(2H, t,             J=6.2Hz), 4.36(1H, m), 6.90(2H, d, J=8.5Hz),             6.92(1H, brs), 6.99-7.31(4H, m), 7.41(2H, d,             J=8.5Hz)     353     1.48-1.64(4H, m), 1.69-1.91(4H, m), 1.91-2.13             (2H, m), 2.21(2H, t, J=6.7Hz), 2.54-3.11(10H,             m), 2.66(6H, s), 3.25(2H, q, J=6.2Hz), 3.70-5.10             (2H, brs), 3.98(2H, t, J=6.2Hz), 4.35(1H, m),             6.15(1H, brs), 6.90(2H, d, J=8.7Hz), 6.99-7.28             (4H, m), 7.41(2H, d, J=8.7Hz)     354     1.37-1.69(4H, m), 1.69-1.94(4H, m), 2.16(3H, s),             2.53-3.20(8H, m), 3.32(2H, q, J=6.5Hz), 3.65-             5.15(2H, br), 3.98(2H, t, J=6.2Hz), 4.54(1H,             m), 4.65(2H, s), 6.51(1H, brs), 6.90(2H, d,             J=8.7Hz), 6.99-7.30(4H, m), 7.42(2H, d, J=8.7Hz)     355     1.49-1.69(4H, m), 1.69-1.98(4H, m), 2.54-3.18             (8H, m), 3.31(2H, q, J=6.3Hz), 3.67(1H, t, J=5.1             Hz), 3.80-5.15(2H, brs), 4.00(2H, t, J=6.2Hz),             4.03(2H, d, J=5.1Hz), 4.37(1H, m), 6.64(1H,             brs), 6.90(2H, d, J=8.7Hz), 6.99-7.28(4H, m),             7.41(2H, d, J=8.7Hz)     356     1.10(3H, t, J=7.1Hz), 1.42-1.70(4H, m), 1.70-             1.95(4H, m), 2.54-3.17(8H, m), 2.61(2H, q, J=7.1             Hz), 3.24(2H, s), 3.30(2H, q, J=6.5Hz), 3.60-             5.20(2H, brs), 3.99(2H, t, J=6.3Hz), 4.37(1H,             m), 6.90(2H, d, J=8.6Hz), 6.99-7.30(4H, m), 7.42             (2H, d, J=8.6Hz), 7.45(1H, brs)     357     1.30-2.00(12H, m), 2.36(2H, m) 2.52-3.20(11H,             m), 3.50-5.15(2H, brs), 3.60-3.84(1H, m), 3.98             (2H, t, J=6.1Hz), 4.22-4.60(2H, m), 6.88(2H, d,             J=8.6Hz), 6.99-7.25(4H, m), 7.40(2H, d, J=8.6Hz)     358     1.49-1.68(4H, m), 1.68-1.95(4H, m), 2.54-3.10             (8H, m), 3.23(2H, d, J=5.1Hz), 3.27(2H, s), 3.31             (2H, q, J=6.3Hz), 3.70-5.10(2H, brs), 3.98(2H,             t, J=6.3Hz), 4.39(1H, m), 5.12(1H, d, J=10.2             Hz), 5.19(1H, d, J=17.2Hz), 5.85(1H, ddt,             J=17.2, 10.2, 5.1Hz), 6.89(2H, d, J=8.7Hz),             6.99-7.38(5H, m), 7.42(2H, d, J=8.7Hz)     359     1.63-1.96(6H, m), 2.54-3.20(8H, m), 3.39(2H, q,             J=6.4Hz), 3.65-5.20(2H, brs), 4.01(2H, t, J=5.8             Hz), 4.05(2H, s), 4.38(1H, m), 6.80(1H, brs),             6.90(2H, d, J=8.7Hz), 6.99-7.25(4H, m), 7.43             (2H, d, J=8.7Hz)     360     1.62-1.98(6H, m), 2.28(6H, s), 2.54-3.14(8H, m),             2.94(2H, s), 3.36(2H, q, J=6.5Hz), 3.70-5.10             (2H, brs), 4.01(2H, t, J=5.9Hz), 4.39(1H, m),             6.90(2H, d, J=8.7Hz), 6.99-7.25(4H, m), 7.27             (1H, brs), 7.43(2H, d, J=8.7Hz)     361     1.03(6H, t, J=7.2Hz), 1.59-1.98(6H, m), 2.43-             3.20(8H, m), 2.55(4H, q, J=7.2Hz), 3.02(2H, s),             3.35(2H, q, J=6.5Hz), 3.70-5.10(2H, brs), 4.02             (2H, t, J=5.9Hz), 4.39(1H, m), 6.90(2H, d, J=8.7             Hz), 6.99-7.29(4H, m), 7.43(2H, d, J=8.7Hz),             7.51(1H, brs)     362     1.60-1.94(6H, m), 2.15(3H, s), 2.54-3.20(8H, m),             3.37(2H, q, J=6.5Hz), 3.80-5.20(2H, brs), 4.00             (2H, t, J=5.8Hz), 4.37(1H, m), 4.55(2H, s), 6.60             (1H, bs), 6.90(2H, d, J=8.5Hz), 7.00-7.28(4H,             m), 7.42(2H, d, J=8.5Hz)     363     1.38-1.72(4H, m), 1.72-1.97(4H, m), 2.30(3H, s),             2.36-3.20(16H, m), 3.01(2H, s), 3.31(2H, q,             J=6.4Hz), 3.70-5.15(2H, brs), 3.99(2H, t, J=6.2             Hz), 4.36(1H, m), 6.90(2H, d, J=8.7Hz), 6.99-             7.30(5H, m), 7.43(2H, d, J=8.7Hz)     364     1.36-1.70(4H, m), 1.70-1.97(4H, m), 2.52-3.15             (8H, m), 2.66(4H, m), 3.06(2H, s), 3.20(4H, m),             3.33(2H, q, J=6.4Hz), 3.75-5.10(2H, brs), 3.98             (2H, t, J=6.1Hz), 4.34(1H, m), 6.60-7.36(11H,             m), 7.40(2H, d, J=8.5Hz)     365     1.56-1.97(6H, m), 2.54-3.22(8H, m), 3.34(2H, q,             J=6.4Hz), 3.70-5.10(2H, brs), 3.98(2H, d, J=5.2             Hz), 4.00(2H, t, J=5.9Hz), 4.35(1H, m), 4.51             (1H, t, J=5.2Hz), 6.89(1H, brs), 6.90(2H, d,             J=8.7Hz), 7.00-7.29(4H, m), 7.40(2H, d, J=8.7Hz)     366     1.05(6H, d, J=6.2Hz), 1.38-1.72(4H, m), 1.72-             1.95(4H, m), 2.54-3.16(9H, m), 3.24(2H, s), 3.30             (2H, q, J=6.3Hz), 3.70-5.20(2H, brs), 3.98(2H,             t, J=6.3Hz), 4.38(1H, m), 6.90(2H, d, J=8.6Hz),             6.99-7.32 94H, m), 7.42(2H, d, J=8.6Hz), 7.49             (1H, brs)     367     1.40-1.69(4H, m), 1.69-1.96(4H, m), 2.54-3.16             (8H, m), 3.29(2H, s), 3.29(2H, q, J=6.3Hz),             3.67-5.20(2H, brs), 3.76(2H, s), 3.97(2H, t,             J=6.3Hz), 4.38(1H, m), 6.88(2H, d, J=8.7Hz),             7.00-7.39(10H, m), 7.41(2H, d, J=8.7Hz)     368     1.37-1.68(4H, m), 1.68-1.98(4H, m), 1.79(4H, m),             2.40-3.15(8H, m), 2.59(4H, m), 3.14(2H, s), 3.31             (2H, q, J=6.4Hz), 3.66-5.20(2H, brs), 3.99(2H,             t, J=6.2Hz), 4.37(1H, m), 6.89(2H, d, J=8.6Hz),             6.98-7.29(5H, m), 7.42(2H, d, J=8.6Hz)     369     1.37-1.71(4H, m), 1.71-1.94(4H, m), 2.35-3.15             (8H, m), 2.52(4H, m), 3.00(2H, s), 3.31(2H, q,             J=6.4Hz), 3.69(4H, m), 3.80-5.20(2H, brs), 3.99             (2H, t, J=6.1Hz), 4.36(1H, m), 6.89(2H d, J=8.6             Hz), 6.98-7.29(5H, m), 7.42(2H, d, J=8.6Hz)     370     1.36-1.69(4H, m), 169-1.95(4H, m), 2.28(3H, s),             2.52-3.13(8H, m), 3.02(2H, s), 3.30(2H, q, J=6.4             Hz), 3.56(2H, s), 3.80-5.20(2H, brs), 3.96(2H,             t, J=6.2Hz), 4.36(1H, m), 6.88(2H, d, J=8.7Hz),             6.98-7.35(5H, m), 7.29(5H, s), 7.42(2H, d, J=8.7Hz)     371     1.38-1.69(4H, m), 1.69-1.94(4H, m), 2.33(3H, s),             2.54-3.17(8H, m), 2.58(2H, t, J=5.2Hz), 3.07             2H, s), 3.29(2H, q, J=6.4Hz), 3.65(2H, t, J=5.2             Hz), 3.80-5.20(2H, br), 3.98(2H, t, J=6.2Hz),             4.38(1H, m), 6.89(2H, d, J=8.7Hz), 6.99-7.28             (4H, m), 7.39(1H, bs), 7.42(2H, d, J=8.7Hz)     372     1.40(3H, t, J=7.0Hz), 1.43-1.68(4H, m), 1.68-             1.93(4H, m), 2.26(3H, s), 2.54-3.10(8H, m), 3.01             (2H, s), 3.30(2H, q, J=6.4Hz), 3.49(2H, s),             3.75-5.10(2H, br), 3.97(2H, t, J=6.2Hz), 4.00             (2H, q, J=7.0Hz), 4.39(1H, m), 6.84(2H, d, J=8.5             Hz), 6.89(2H, d, J=8.6Hz), 6.99-7.28(5H, m),             7.18(2H, d, J=8.5Hz), 7.42(2H, d, J=8.6Hz)     373     1.32-1.65(4H, m), 1.65-1.93(4H, m), 2.53-3.14             (8H, m), 3.24(2H, q, J=6.2Hz), 3.60-5.10(2H,             brs), 3.82(2H, d, J=5.7Hz), 3.94(2H, t, J=6.2             Hz), 4.37(1H, m), 5.11(2H, s), 5.79(1H, brs),             6.48(1H, brs), 6.88(2H, d, J=8.7Hz), 6.99-7.36             (4H, m), 7.33(5H, s), 7.41(2H, d, J=8.7Hz)     374     1.42-2.02(12H, m), 2.36(2H, t, J=7.4Hz), 2.38             (1H, m), 2.54-3.16(10H, m), 3.53-5.15(2H, brs),             3.76-3.97(1H, m), 4.00(2H, t, J=6.3Hz), 4.38             (1H, m), 4.48-4.67(1H, m), 5.58(1H, brs), 5.81             (1H, brs), 6.90(2H, d, J=8.7Hz), 6.99-7.29(4H,             m), 7.42(2H, d, J=8.7.Hz)     375     1.45-1.98(10H, m), 2.23(1H, m), 2.54-3.10(10H,             m), 3.12(1H, m), 3.18,(1H, m), 3.32(2H, q, J=6.4             Hz), 3.70-5.20(2H, brs), 4.00(2H, t, J=5.8Hz),             4.37(1H, m), 5.95(1H, brs), 6.90(2H, d, J=8.7             Hz), 6.99-7.28(4H, m), 7.42(2H, d, J=8.7Hz)     376     1.44-2.02(10H, m), 2.09(3H, s), 2.29(1H, m),             2.54-3.20(10H, m), 3.32(2H, q, J=6.4Hz), 3.70-             5.20(2H, brs), 3.78-3.94(1H, m), 4.00(2H, t,             J=5.8Hz), 4.36(1H, m), 4.52-4.69(1H, m), 5.87             (1H, brs), 6.89(2H, d, J=8.7Hz), 6.99-7.28(4H,             m), 7.42(2H, d, J=8.7Hz)     377     1.42-2.01(12H, m), 2.38(2H, t, J=7.3Hz), 2.52-             3.26(11H, m), 2.94(3H, s), 3.09(3H, s), 3.65-             5.20(2H, brs), 3.82-4.14(1H, m), 4.00(2H, t,             J=6.2Hz), 4.36(1H, m), 4.53-4.74(1H, m), 6.91             (2H, d, J=8.6Hz), 6.98-7.29(4H, m), 7.42(2H, d,             J=8.6Hz)     378     1.37-1.71(4H, m), 1.71-1.90(4H, m), 2.53-3.16             (8H, m), 3.30(2H, q, J=6.3Hz), 3.32(2H, s),             3.70-5.20(2H, brs), 3.98(2H, t, J=6.1Hz), 4.35             (1H, m), 6.90(2H, d, J=8.5Hz), 6.99-7.29(4H, m),             7.42(2H, d, J=8.5Hz), 7.44(1H, bs)     379     1.33-1.67(4H, m), 1.67-2.00(4H, m), 2.53-3.15             (8H, m), 2.96(3H, s), 3.24(2H, q, J=6.2Hz),             3.50-5.30(2H, brs), 3.71(2H, d, J=5.8Hz), 3.97             (2H, t, J=6.2Hz), 4.36(1H, m), 6.11(1H, t, J=5.8             Hz), 6.88(1H, brs), 6.90(2H, d, J=8.7Hz), 6.99-             7.29(4H, m), 7.41(2H, d, J=8.7Hz)     380     1.41-2.10(8H, m), 2.53-3.30(8H, m), 3.47(2H, q,             J=6.2Hz), 3.70-5.20(2H, brs), 3.97(2H, t, J=6.2             Hz), 4.34(1H, m), 6.87(2H, d, J=8.7Hz), 6.99-             7.29(5H, m), 7.39(2H, d, J=8.7Hz), 7.96(2H, dd,             J=6.9, 2.0Hz), 8.22(2H, dd, J=6.9, 2.0Hz)     381     1.41-1.73(4H, m), 1.73-2.02(4H, m), 2.53-3.20             (8H, m), 3.43(2H, q, J=6.4Hz), 3.70-5.20(2H,             br), 3.97(2H, t, J=6.2Hz), 4.36(1H, m), 6.40             (1H, brs), 6.62(2H, d, J=8.5Hz), 6.87(2H, d,             J=8.5Hz), 6.99-7.28(4H, m), 7.40(2H, d, J=8.5             Hz), 7.60(2H, d, J=8.5Hz)     382     1.30-1.63(4H, m), 1.63-2.05(4H, m), 2.55-3.30             (8H, m), 3.00(2H, q, J=6.2Hz), 3.70-5.20(2H,             brs), 3.90(2H, t, J=6.2Hz), 4.37(1H, m), 5.50             (1H, t, J=6.2Hz), 6.86(2H, d, J=8.7Hz), 7.00-             7.29(4H, m), 7.41(2H, d, J=8.7Hz), 8.04(2H, dd,             J=6.9, 2.0Hz), 8.33(2H, dd, J=6.9, 2.0Hz),     383     1.40-1.95(8H, m), 2.15(3H, s), 2.54-3.20(8H, m),             3.44(2H, q, J=6.1Hz), 3.70-5.20(2H, brs), 3.95             (2H, t, J=6.1Hz), 4.33(1H, m), 6.76(1H, brs),             6.83(2H, d, J=8.7Hz), 7.00-7.30(4H, m), 7.34             (2H, d, J=8.7Hz), 7.53(2H, d, J=8.7Hz), 7.68             (2H, d, J=8.7Hz), 8.73(1H, brs)     384     1.40-1.95(8H, 2.54-3.11(8H, m), 3.01(6H,             s), 3.46(2H, q, J=6.5Hz), 3.80-5.30(2H, brs),             3.98(2H, t, J=6.3Hz), 4.39(1H, m), 6.14(1H,             brs), 6.65(2H, dd, J=6.9, 2.1Hz), 6.89(2H, d,             J=8.8Hz), 6.99-7.28(4H, m), 7.42(2H, d, J=8.8             Hz), 7.67(2H, dd, J=6.9, 2.1Hz)     385     1.26-1.61(4H, m), 1.61-2.00(4H, m), 2.54-3.30             (8H, m), 2.91(2H, q, J=6.0Hz), 3.70-5.20(2H,             brs), 3.90(2H, t, J=6.2Hz), 4.34(1H, m), 4.91             (1H, brs), 6.60(2H, d, J=8.6Hz), 6.85(2H, d,             J=8.6Hz), 6.99-7.29(4H, m), 7.40(2H, d, J=8.6             Hz), 7.58(2H, d, J=8.6Hz)     386     1.48-1.74(4H, m), 1.74-2.02(4H, m), 2.23(3H, s),             2.28(3H, s), 2.54-3.30(8H, m), 3.65-5.20(2H,             brs), 3.79(2H, t, J=7.4Hz), 4.00(2H, t, J=5.9             Hz), 4.35(1H, m), 6.91(2H, d, J=8.7Hz), 7.00-             7.30(4H, m), 7.41(2H, d, J=8.7Hz), 7.46(2H, d,             J=8.4Hz), 7.65(2H, d, J=8.4Hz), 9.23(1H, s)     387     1.33-1.64(4H, m), 1.64-1.93(4H, m), 2.54-3.15             (8H, m), 2.92(2H, q, J=6.5Hz), 3.02(6H, s),             3.70-5.20(2H, brs), 3.90(2H, t, J=6.3Hz), 4.38             (1H, m), 4.81(1H, t, J=6.5Hz), 6.66(2H, d, J=9.1             Hz), 6.86(2H, d, J=8.7Hz), 6.99-7.28(4H, m),             7.41(2H, d, J=8.7Hz), 7.69(2H, d, J=9.1Hz)     388     1.02(6H, t, J=7.1Hz), 1.34-1.93(8H, m), 2.37-             3.12(10H, m), 2.52(4H, q, J=7.1Hz), 3.86-5.08             (3H, m), 3.98(2H, t, J=6.5Hz), 7.83-7.49(8H, m)     389     1.42-1.96(12H, m), 2.35-3.15(14H, m), 3.78-5.13             (3H, m), 3.98(2H, t, J=6.4Hz), 6.82-7.50(8H, m)     390     1.35-1.93(8H, m), 2.15-3.15(10H, m), 3.32-3.78             (3H, m), 3.83-5.22(3H, m), 3.97(2H, t, J=6.3Hz),             6.79-7.48(8H, m)     391     1.38-1.93(8H, m), 2.43-3.40(12H, m), 3.65-5.15             (4H, m), 3.81(3H, s), 3.84(2H, s), 3.97(2H, t,             J=6.2Hz), 6.75-7.48(12H, m)     392     1.30-1.96(6H, m), 2.49-3.62(16H, m), 3.68-5.05             (4H, m), 3.98(2H, t, J=6.2Hz), 6.78-7.52(8H, m),             7.62(1H, dt, J=7.7, 1.8Hz), 8.43-8.59(1H, m)     393     1.18-1.95(14H, m), 2.13-3.10(16H, m), 3.56-5.14             (4H, m), 3.99(2H, t, J=6.3Hz), 6.83-7.48(13H, m),     394     1.60-1.93(6H, m), 2.27-3.14(18H, m), 3.02(2H, d,             J=6.6Hz), 3.75-5.05(3H, m), 4.00(2H, t, J=6.2             Hz), 5.12-5.26(2H, m), 5.78-5.98(1H, m), 6.81-             7.47(8H, m)     395     1.32-2.03(8H, m), 2.33(3H, s), 2.28-3.13(15H,             m), 3.52-5.15(4H, m), 3.98(2H, t, J=6.3Hz),             6.83-7.48(10H, m), 7.60(1H, dt, J=7.6, 1.8Hz),             8.50-8.57(1H, m)     396     1.06(3H, t, J=6.7Hz), 1.20-1.96(8H, m), 2.28-             3.15(12H, m), 3.22-5.08(5H, m), 3.46(1H, d,             J=14.4Hz), 3.83(1H, d, J=14.4Hz), 3.99(2H, t,             J=6.7Hz), 6.83-7.52(10H, m), 8.52-8.62(1H, m)     397     1.25-1.62(8H, m), 1.65-1.93(8H, m), 2.36-3.13             (14H, m), 3.80-5.05(3H, m), 3.97(2H, t, J=6.5             Hz), 6.83-7.49(8H, m)     398     1.09(6H, t, J=7.2Hz), 1.22-1.93(12H, m), 2.4-             3.12(10H, m), 2.63(4H, q, J=7.2Hz), 3.12-5.11             (3H, m), 3.98(2H, t, J=6.6Hz), 6.84-7.48(8H, m)     399     1.63-2.03(10H, m), 2.48-3.13(14H, m), 3.82-5.03             (3H, m), 4.01(2H, t, J=5.9Hz), 6.81-7.49(8H, m)     400     1.05(6H, t, J=7.2Hz), 1.57-1.90(6H, m), 2.42-             3.15(14H, m), 3.83-5.04(3H, m), 4.01(2H, t,             J=6.4Hz), 6.83-7.48(8H, m)     401     1.25-1.93(10H, m), 2.36(3H, s), 2.43-3.12(17H,             m), 3.82-5.16(3H, m), 3.97(2H, t, J=6.4Hz),             6.85-7.48(10H, m), 7.60(1H, dt, J=7.6, 1.9Hz),             8.49-8.55(1H, m)     402     1.35-3.35(26H, m), 3.62-4.42(5H, m), 3.99(2H, t,             J=6.6Hz), 5.57(1H, brs), 6.83-7.47(8H, m),     403     1.42-2.08(12H, m), 2.43-3.44(15H, m), 3.82-5.04             (4H, m), 3.99(2H, t, J=6.2Hz), 6.83-7.49(8H, m)     404     1.32-1.93(8H, m), 2.25(2H, brs), 2.50-3.13(10H,             m), 3.80-5.00(4H, m), 3.92(2H, s), 3.97(2H, t,             J=6.5Hz), 6.82-7.48(10H, m), 7.65(1H, dt, J=7.6,             1.8Hz), 8.51-8.59(1H, m)     405     1.32-1.92(10H, m), 2.48-3.17(10H, m), 3.72-5.18             (4H, m), 3.82(2H, s), 3.97(2H, t, J=6.4Hz),             6.83-7.49(9H, m), 7.65-7.75(1H, m), 8.50(1H, dd,             J=4.8, 1.6Hz), 8.56(1H, d, J=1.8Hz)     406     1.13-1.92(14H, m), 2.18-3.12(14H, m), 3.47(1H,             dd, J=10.7, 4.1Hz), 3.75(1H, dd, J=10.7, 3.8Hz),             3.81-5.08(3H, m), 3.98(2H, t, J=6.4Hz), 6.83-             7.48(8H, m)     407     1.40-2.03(12H, m), 2.25-3.15(13H, m), 3.20-3.31             (1H, m), 3.45(1H, dd, J=11.0, 3.0Hz), 3.67(1H,             dd, J=11.0, 3.6Hz), 3.75-5.13(3H, m), 3.99(2H,             t, J=6.3Hz), 6.83-7.50(8H, m)     408     1.07-1.93(13H, m), 1.96-3.13(15H, m), 3.53(1H,             dd, J=10.5, 5.8Hz), 3.66(1H, dd, J=10.5, 5.0Hz),             3.74-5.13(3H, m), 3.98(2H, t, J=6.4Hz), 6.83-             7.47(8H, m)     409     1.42-1.93(8H, m), 2.12-3.14(17H, m), 3.83-5.14             (4H, m), 3.99(2H, t, J=6.4Hz), 6.83-6.96(2H, m),             6.96-7.32(4H, m), 7.33-7.48(2H, m)     ______________________________________     No.     NMR (DMSO-d.sub.6) δ value     ______________________________________     410     1.33-1.97(15H, m), 2.38-3.28(14H, m), 3.48(2H,             t, J=6.3Hz), 3.90-4.83(3H, m), 4.07(2H, t, J=6.2             Hz), 6.95-7.49(8H, m), 10.30(1H, brs)     ______________________________________     No.     NMR (CDCl.sub.3) δ value     ______________________________________     411     1.40-1.66(4H, m), 1.68-2.22(8H, m), 2.26-3.28             (13H, m), 3.72(3H, s), 3.78-5.10(3H, m), 3.97             (2H, t, J=6.4Hz), 6.83-7.48(8H, m)     ______________________________________     No.     NMR (DMSO-d.sub.6) δ value     ______________________________________     412     1.30-2.13(16H, m), 2.33-3.60(16H, m), 3.62-4.93             (3H, m), 4.02(2H, t, J=6.2Hz), 6.87-7.05(3H, m),             7.18-7.42(5H, m), 10.03(1H, brs)     ______________________________________     No.     NMR (CDCl.sub.3) δ value     ______________________________________     413     1.43-1.93(8H, m), 2.35-3.12(14H, m), 3.67-5.24             (3H, m), 3.84(4H, t, J=5.3Hz), 4.00(2H, t, J=6.4             Hz), 6.47(1H, t, J=4.7Hz), 6.84-7.50(8H, m),             8.30(2H, d, J=4.7Hz)     414     1.40-1.96(8H, m), 2.34-3.13(14H, m), 3.55(4H, t,             J=4.8Hz), 3.75-5.21(3H, m), 4.00(2H, t, J=6.4             Hz), 6.55-6.67(2H, m), 6.85-7.53(9H, m), 8.12-             8.22(1H, m)     415     1.40-1.93(8H, m), 2.28(3H, s), 2.41-3.12(13H,             m), 3.61(2H, t, J=5.5Hz), 3.75-5.25(3H, m), 3.99             (2H, t, J=6.4Hz), 6.85-7.49(8H, m)     416     1.37-2.04(12H, m), 2.22-3.16(13H, m), 3.18-3.34             (1H, m), 3.45(1H, dd, J=11.0, 2.8Hz), 3.67(1H,             dd, J=11.0, 3.5Hz), 3.85-5.23(3H, m), 3.99(2H,             t, J=6.3Hz), 6.83-7.50(8H, m)     417     1.38-1.93(8H, m), 2.28-3.13(16H, m), 3.63(4H, t,             J=5.4Hz), 3.77-5.08(3H, m), 3.99(2H, t, J=6.3             Hz), 6.85-7.50(8H, m)     418     1.38(6H, dt, J=7.1, 2.5Hz), 1.42-1.98(8H, m),             2.49-3.14(8H, m), 3.22-3.41(1H, m), 3.27(3H, s),             3.39(3H, s), 3.48-5.13(9H, m), 4.04(2H, t, J=6.2             Hz), 6.83-7.47(8H, m)     419     1.38-1.95(8H, m), 2.27(3H, s), 2.36-3.19(14H,             m), 3.78-5.06(3H, m), 3.99(2H, t, J=6.4Hz),             6.85-6.95(2H, m), 6.97-7.32(4H, m), 7.37-7.48             (2H, m)     420     1.32-1.97(14H, m), 1.12-3.21(15H, m), 3.58-5.06             (4H, m), 3.99(2H, t, J=6.4Hz), 6.83-7.54(8H, m)     421     1.51-2.00(8H, m), 2.47-3.28(8H, m), 3.18(2H, t,             J=6.8Hz), 3.79-5.15(3H, m), 4.00(2H, t, J=6.1             Hz), 6.78-3.37(7H, m), 7.42(2H, d, J=8.7Hz),             8.50(2H, d, J=4.8Hz)     422     1.45-2.17(8H, m), 2.44-3.24(10H, m), 3.61(3H,             s), 3.80-5.12(3H, m), 3.97(2H, t, J=6.3Hz),             6.80-7.38(8H, m), 7.42(2H, d, J=8.7Hz)     423     1.52-2.04(8H, m), 2.49-3.15(8H, m), 3.38-3.57             (2H, m), 3.75-5.12(8H, m), 6.88(2H, d, J=8.7Hz),             6.93-7.36(6H, m), 7.42(2H, d, J=8.7Hz)     424     1.47-2.20(8H, m), 2.48-3.33(10H, m), 3.75-5.14             (5H, m), 6.87(2H, d, J=8.7Hz), 6.93-7.54(7H, m),             8.88(2H, d, J=4.9Hz)     425     1.52-2.13(8H, m), 2.49-3.14(8H, m), 3.47-3.68             (2H, m), 3.85-5.11(3H, m), 3.99(2H, t, J=6.1Hz),             6.87(2H, d, J=8.8Hz), 6.93-7.38(4H, m), 7.42             (2H, d, J=8.8.Hz), 7.57(1H, d, J=4.9Hz), 8.95             (1H, d, J=4.9Hz)     426     1.09-2.02(10H, m), 2.42-5.21(29H, m), 6.89(2H,             d, J=8.7Hz), 6.94-7.36(4H, m), 7.40(2H, d, J=8.7Hz)     427     1.38(9H, t, J=7.1Hz), 1.48-2.19(8H, m), 2.49-             3.16(8H, m), 3.27-3.45(2H, m), 3.50(6H, q, J=7.1             Hz), 3.80-5.11(3H, m), 4.03(2H, t, J=4.7Hz),             6.90(2H, d, J=8.6Hz), 6.97-3.38(4H, m), 7.41             (2H, d, J=8.6Hz)     428     1.34-3.39(25H, m), 3.77-5.12(3H, m), 3.97(2H, t,             J=6.3Hz), 5.57-5.92(3H, m), 6.88(2H, d, J=8.8             Hz), 6.94-7.36(4H, m), 7.42(2H, d, J=8.8Hz)     429     1.35-1.99(8H, m), 2.42-3.20(8H, m), 3.72-5.15             (3H, m), 3.97(4H, t like, J=6.9Hz), 6.81-7.62             (11H, m)     430     1.37-2.14(8H, m), 2.45-3.16(8H, m), 3.71-5.15             (3H, m), 3.98(2H, t, J=6.2Hz), 4.21(2H, t, J=7.0             Hz), 6.78-7.52(8H, m), 7.94(1H, s), 8.07(1H, s)     431     1.53-2.01(8H, m), 2.48-3.17(10H, m), 3.80-5.12             (3H, m), 4.00(2H, t, J=6Hz), 6.89(2H, d, J=8.8             Hz), 6.92-7.55(8H, m), 6.05-8.22(2H, m)     432     1.22-1.96(14H, m), 2.46-3.16(8H, m), 3.75-5.18             (3H, m), 3.68(2H, t, J=7.2Hz), 3.96(2H, t, J=6.5             Hz), 6.89(2H, d, J=8.7Hz), 6.94-7.36(4H, m),             7.42(2H, d, J=8.7Hz), 7.63-7.92(4H, m)     433     1.40-2.02(8H, m), 2.41-3.22(10H, m), 3.50-5.15,             (3H, m), 3.76(2H, brs), 3.95(2H, t, J=6 2.Hz),             6.48-6.68(2H, m), 6.87(2H, d, J=8.8Hz); 6.94-             7.37(6H, m), 7.42(2H, d, J=8.8Hz)     434     1.44-2.11(8H, m), 2.50-3.32(10H, m), 3.83-5.10             (3H, m), 3.96(2H, t, J=5.8Hz), 6.85(2H, d, J=8.7             Hz), 6.90-7.38(4H, m), 7.41(2H, d, J=8.7Hz),             8.05-8.21(2H, m), 8.36-8.52(2H, m)     435     1.41-2.12(8H, m), 2.45-3.41(8H, m), 3.20(2H, t,             J=6.9Hz), 3.70-5.11(3H, m), 3.99(3H, t, J=6.3             Hz), 6.75-7.17(11H, m), 8.37-8.52(2H, m)     436     1.51-2.05(8H, m), 2.37-3.22(10H, m), 3.76-5.14             (3H, m), 4.00(2H, t, J=6.1Hz), 6.89(2H, d, J=8.7             Hz), 6.95-7.38(6H, m), 7.43(2H, d, J=8.7Hz),             8.30-8.49(2H, m)     437     1.41-1.92(8H, m), 2.47-3.19(10H, m), 3.70-5.10             (5H, m), 3.93(2H, t, J=6Hz), 6.56-7.70(12H, m)     438     1.46-2.02(8H, m), 2.43-3.19(8H, m), 3.31-3.56             (2H, m), 3.70-5.11(3H, m), 3.96(2H, t, J=5.9Hz),             6.75-7.51(8H, m), 7.56(1H, ddd, J=1.3, 4.7, 7.6             Hz), 7.89-8.18(2H, m), 8.68-8.81(1H, m)     439     1.48-1.97(8H, m), 2.47-3.30(10H, m), 3.78-5.12             (5H, m), 6.87(2H, d, J=8.7Hz), 6.94-7.36(4H, m),             7.43(2H, d, J=8.7Hz), 7.68-7.88(2H, m), 8.23-             8.39(2H, m)     440     1.41-2.01(8H, m), 2.25(3H, s,), 2.48-3.16(10H,             m), 3.71-5.18(3H, m), 3.90(2H, d, J=5.5Hz), 6.78             (2H, d, J=8.7Hz), 6.98-7.54(8H, m), 7.63(2H, d,             J=8.7Hz), 9.03(1H, brs)     441     1.15-2.16(16H, m), 2.44-3.13(10H, m), 3.75-5.20             (3H, m), 3.98(2H, t, J=6.5Hz), 6.90(2H, d, J=8.7             Hz), 6.94-7.37(4H, m), 7.42(2H, d, J=8.7Hz)     442     1.22-5.20(34H, m), 5.92-6.19(1H, m), 6.90(2H, d,             J=8.5Hz), 6.95-7.34(4H, m), 7.42(2H, d, J=8.5Hz),     443     1.42-1.96(8H, m), 2.50-3.19(10H, m), 3.06(6H,             s), 3.74-5.11(3H, m), 3.94(2H, t, J=6.2Hz), 6.69             (2H, d, J=9.1Hz), 6.85(2H, d, J=8.8Hz), 6.92-             7.34(4H, m), 7.40(2H, d, J=8.8Hz), 7.69(2H, d,             J=9.1Hz)     444     1.20-2.02(14H, m), 1.97(3H, m), 2.48-3.32(10H,             m), 3.77-5.15(3H, m), 3.98(2H, t, J=6.4Hz), 5.61             (1H, brs), 6.90(2H, d, J=8.7Hz), 6.98-7.38(4H,             m), 7.42(2H, d, J=8.7Hz)     445     1.29-3.40(25H, m), 2.03(3H, s), 2.07(3H, s),             3.81-5.15(7H, m), 5.76(brs), 6.89(2H, d, J=8.4             Hz), 6.96-7.51(6H, m)     446     1.62-1.94(2H, m), 1.99(3H, s), 2.01(2H, m),             2.46-3.20(8H, m), 3.45(2H, q, J=6.3Hz), 3.70-             5.20(2H, brs), 4.05(2H, t, J=5.9Hz), 4.34(1H,             m), 6.00(1H, brs), 6.60(1H, d, J=8.1Hz), 6.67             (1H, d, J=8.1Hz), 6.89(2H, d, J=8.7Hz), 7.10             (1H, t, J=8.1Hz), 7.42(2H, d, J=8.7Hz)     447     1.42(3H, t, J=7.0Hz), 1.57-1.75(1H, m), 1.75-             1.93(1H, m), 2.40-3.24(8H, m), 3.56-3.92(4H, m),             4.04(2H, q, J=7.0Hz), 4.19-4.66(1H, m), 4.80-             5.04(1H, m), 6.37-6.67(1H, m), 6.48(1H, d, J=8.1             Hz), 6.60-6.78(1H, m), 6.61(1H, d, J=8.1Hz),             7.01(1H, t, J=8.1Hz), 7.10-7.46(1H, m), 8.36             (1H, brs)     448     1.42(3H, t, J=7.0Hz), 1.57-1.75(1H, m), 1.75-             1.94(1H, m), 2.35-3.20(8H, m), 3.57-3.73(1H, m),             3.73-3.92(3H, m), 3.84(3H, s), 4.04(2H, q, J=7.0             Hz), 4.25-4.75(1H, m), 4.86-5.04(1H, m), 6.43-             6.57(1H, m), 6.50(1H, d, J=8.2Hz), 6.64(1H, d,             J=8.2Hz), 6.68-6.91(1H, m), 7.12-7.33(1H, m),             7.18(1H, t, J=8.2Hz)     449     1.42(3H, t, J=6.9Hz), 1.66-1.91(2H, m), 1.91-             2.13(2H, m), 1.97(3H, s), 2.47-3.20(8H, m), 3.42             (2H, q, J=6.3Hz), 3.80-5.20(2H, brs), 4.03(2H,             t, J=6.9Hz), 4.05(2H, q, J=6.9Hz), 4.35(1H, m),             6.37(1H, brs), 6.64(1H, d, J=8.2Hz), 6.74(1H,             d, J=8.2Hz), 6.89(2H, d, J=8.7Hz), 7.17(1H, t,             J=8.2Hz), 7.42(2H, d, J=8.7Hz)     450     1.42(6H, t, J=7.0Hz), 1.55-1.76(1H, m), 1.76-             1.93(1H, m), 2.35-3.22(8H, m), 3.50-3.75(1H, m),             3.75-3.94(3H, m), 4.04(4H, q, J=7.0Hz), 4.26-             4.72(1H, m), 4.82-5.05(1H, m), 6.49-6.58(1H, m),             6.51(1H, d, J=8.2Hz), 6.63(1H, d, J=8.2Hz),             6.68-6.92(1H, m), 7.15(1H, t, J=8.2Hz), 7.20-             7.35(1H, m)     451     1.42(3H, t, J=7.0Hz), 1.55-1.75(1H, m), 1.75-             1.98(1H, m), 2.33(3H, s), 2.41-3.23(8H, m),             3.53-3.96(4H, m), 4.05(2H, q, J=7.0Hz), 4.18-             4.68(1H, m), 4.86-5.08(1H, m), 6.46-6.60(1H, m),             6.49(1H, d, J=8.0Hz), 6.81(1H, d, J=8.0Hz),             6.94-7.32(2H, m), 7.24(1H, t, J=8.0Hz)     452     1.55-1.88(2H, m), 1.88-2.10(2H, m), 1.97(3H, s),             2.47-3.20(8H, m), 3.42(2H, q, J=6.3Hz), 3.60-             5.20(2H, brs), 3.84(3H, s), 4.03(2H, t, J=6.0             Hz), 4.34(1H, m), 6.30(1H, brs), 6.65(1H, d,             J=8.3Hz), 6.75(1H, d, J=8.3Hz), 6.89(2H, d,             J=8.7Hz), 7.20(1H, t, J=8.3Hz), 7.41(2H, d,             J=8.7Hz)     453     1.67-1.93(2H, m), 1.93-2.11(2H, m), 1.98(3H, s),             2.33(3H, s), 2.50-3.15(8H, m), 3.43(2H, q, J=6.4             Hz), 3.80-5.20(2H, br), 4.04(2H, t, J=5.9Hz),             4.33(1H, m), 6.13(1H, brs), 6.82(1H, d, J=8.1             Hz), 6.90(2H, d, J=8.7Hz), 7.01(1H, d, J=8.1             Hz), 7.26(1H, t, J=8.1Hz), 7.42(2H, d, J=8.7Hz)     454     1.60-1.90(3H, m), 2.40-2.95(8H, m), 3.10-3.36             (2H, m), 4.23-4.48(1H, m), 6.70-7.22(3H, m)     455     1.55-1.93(2H, m), 2.35-3.27(8H, m), 3.58-4.00             (7H, m), 4.25-4.74(1H, m), 4.86-5.07(1H, m),             6.44-6.60(2H, m), 6.73-7.37(4H, m)     456     1.42(3H, t, J=7.0Hz), 1.55-1.90(2H, m), 2.35-             3.20(8H, m), 3.60-3.93(4H, m), 4.01.(2H, q, J=7.0             Hz), 4.25-4.70(1H, m), 4.85-5.05(1H, m), 6.40-             6.59(2H, m), 6.72-7.35(4H, m)     457     1.70-2.12(4H, m), 1.95(3H, s), 2.31(3H, s),             2.42-3.15(8H, m), 3.35-3.50(2H, m), 3.80-5.10             (5H, m), 6.17(1H, brs), 6.80-7.20(5H, m), 7.42             (2H, d, J=8.5Hz)     458     1.40-2.05(10H, m), 2.31(3H, s), 2.42-3.20(8H,             m), 3.43(2H, t, J=6.7Hz), 3.70-5.05(5H, m),             6.80-7.22(5H, m), 7.42(2H, d, J=8.7Hz)     459     1.03(6H, t, J=7.1Hz), 1.22-2.00(10H, m), 2.31             (3H, s), 2.40-3.23(14H, m), 3.80-5.21(5H, m),             6.85-7.20(5H, m), 7.42(2H, d, J=8.7Hz)     460     1.30-2.15(14H, m), 2.31(3H, s), 2.38-3.20(14H,             m), 3.80-5.05(5H, m), 6.80-7.22(5H, m), 7.42(2H,             d, J=8.7Hz)     461     1.42-1.96(8H, m), 2.42-3.13(12H, m), 3.30(2H, d,             J=6.1Hz), 3.98(2H, t, J=6.3Hz), 3.80-4.97(3H,             m), 4.98-5.28(2H, m), 5.83-6.04(1H, m), 6.82-7.48             (8H, m)     462     1.34-1.95(9H, m), 2.45-3.15(12H, m), 3.57(2H, t             J=5.4Hz), 3.63(2H, s), 3.95(2H, t, J=6.3Hz),             3.78-5.14(3H, m), 6.84-7.50(13H, m)     463     1.07(3H, d, J=6.3Hz), 1.24-1.93(14H, m), 2.07-             2.48(3H, m), 2.53-3.13(10H, m), 3.98(2H, t,             J=6.4Hz), 3.82-5.10(3H, m), 6.84-7.50(8H, m)     464     0.76-0.95(1H, m), 0.87(3H, d, J=6.1Hz), 1.38-             1.93(14H, m), 2.27-2.41(2H, m), 2.52-3.12(10H,             m), 3.98(2H, t, J=6.4Hz), 3.83-5.07(3H, m),             6.83-7.49(8H, m)     465     0.92(3H, d, J=5.8Hz), 1.14-2.02(15H, m), 2.26-             2.42(2H, m), 2.52-3.13(10H, m), 3.98(2H, t,             J=6.4Hz), 3.86-5.06(3H, m), 6.83-7.52(8H, m)     466     1.43-1.93(8H, m), 2.52-3.13(14H, m), 3.69(2H, t,             J=5.3Hz), 3.99(2H, t, J=6.3Hz), 3.80-5.05(3H,             m), 6.83-7.49(8H, m)     467     1.04(6H, t, J=7.2Hz), 1.33-2.05(8H, m), 2.30-             3.22(14H, m), 3.54-3.75(1H, m), 3.93-4.20(2H,             m), 4.30-4.42(1H, m), 4.93-5.07(1H, m), 6.83-7.42             (8H, m)     468     1.36-1.92(8H, m), 2.28(6H, s), 2.42-3.13(14H,             m), 3.60(2H, s), 3.72-5.07(3H, m), 3.96(2H, t,             J=6.4Hz), 6.85-7.48(13H, m)     469     1.45-1.98(14H, m), 2.49-3.14(14H, m), 3.82-5.13             (3H, m), 3.99(2H, t, J=6.2Hz), 6.82-7.49(8H, m)     470     1.38-1.94(8H, m), 2.22(3H, s), 2.28-2.44(2H, m),             2.49-3.10(8H, m), 3.00(2H, d, J=6.5Hz), 3.88-             4.96(3H, m), 3.98(2H, t, J=6.4Hz), 5.08-5.24             (2H, m), 5.87(1H, ddt, J=17.1, 10.2, 6.5Hz),             6.83-7.49(8H, m)     471     1.40-1.92(8H, m), 2.05, 2.07, 2.12, 2.14(total:             6H, s), 2.52-3.14(8H, m), 3.28-3.43(2H, m), 3.55             (2H, dt, J=8.5, 5.9Hz), 3.99(2H, dt, J=6.1, 6.1             Hz), 4.20(2H, dt, J=6.0, 6.0Hz). 3.84-4.98(3H,             m), 6.85-7.50(8H, m)     472     1.38-1.93(8H, m), 2.07(3H, s), 2.31(3H, s),             2.37-3.13(12H, m), 3.87-5.04(3H, m), 3.98(2H, t,             J=6.4Hz), 4.18(2H, t, J=5.9Hz), 6.84-7.49(8H, m)     473     1.37-1.94(8H, m), 2.05(6H, s), 2.49-3.12(10H,             m), 2.77(4H, t, J=6.2Hz), 3.83-5.05(3H, m), 3.98             (2H, t, J=6.3Hz), 4.12(4H, t, J=6.1Hz), 6.85-             7.48(8H, m)     474     1.13(6H, d, J=6.3Hz), 1.40-1.93(8H, m), 2.49-             3.13(12H, m), 3.84-5.03(3H, m), 3.98(2H, t,             J=6.4Hz), 6.84-7.48(8H, m)     475     1.44-2.08(8H, m), 2.02-3.30(10H, m), 3.09(3H,             s), 3.77-5.02(3H, m), 3.87(2H, d, J=7.1Hz), 4.00             (2H, d, J=6.1Hz), 5.41-5.08(2H, m), 6.03-6.27             (1H, m), 6.83-7.48(8H, m)     476     1.00(6H, t, J=7.1Hz), 1.41-1.93(8H, m), 2.05             (3H, s), 2.32-3.13(14H, m), 3.86-5.05(3H, m),             3.98(2H, t, J=6.3Hz), 4.90-5.03(1H, m), 6.85-             7.48(8H, m)     477     1.38-1.93(12H, m), 2.37-3.13(14H, m), 3.87-5.05             (3H, m), 4.01(2H, t, J=6.4Hz), 6.83-7.49(8H, m)     478     1.28-1.93(16H, m), 2.32-3.11(14H, m), 3.83-5.07             (3H, m), 3.97(2H, t, J=6.4Hz), 6.85-7.51(8H, m)     479     1.43-1.96(8H, m), 2.26(6H, s), 2.26-2.42(2H, m),             2.53-3.07(8H, m), 3.91-5.04(3H, m), 3.99(2H, t,             J=6.4Hz), 6.86-7.47(8H, m)     480     1.30-1.92(10H, m), 2.30(6H, s), 2.27-2.43(2H,             m), 2.53-3.12(8H, m), 3.87-4.87(3H, m), 3.98(2H,             t, J=6.4Hz), 6.85-7.48(8H, m)     481     1.55-2.16(7H, m), 2.37-5.37(17H, m), 6.38-7.59             (13H, m)     482     1.26(3H, t, J=7.2Hz), 1.52-2.01(6H, m), 2.32-             3.33(10H, m), 3.53-5.10(8H, m), 4.14(2H, q,             J=7.2Hz), 6.40-6.58(2H, m), 6.96-7.33(5H, m)     483     1.58-3.32(16H, m), 3.56-5.12(8H, m), 5.52-6.00             (2H, m), 6.48-6.60(2H, m), 6.95-7.48(5H, m)     484     1.35-5.15(49H, m), 6.36-6.60(2H, m), 6.92-7.38             (5H, m)     485     1.27-4.61(52H, m), 4.78-5.06(1H, m), 6.34-6.60             (2H, m), 6.93-7.40(5H, m)     ______________________________________     No.     NMR (DMSO.sub.6) δ value     ______________________________________     486     1.24(12H, t, J=7.2Hz), 1.31-2.12(14H, m), 2.25-             4.43(26H, m), 4.55-4.79(1H, m), 6.48-6.72(2H,             m), 6.94-7.43(5H, m), 10.49-10.97(2H, m)     ______________________________________     No.     NMR (CDCl.sub.3) δ value     ______________________________________     487     1.51-2.02(6H, m), 2.18-4.13(27H, m), 4.28-4.72             (1H, m), 4.88-5.08(1H, m), 6.37-6.59(2H, m),             6.92-7.38(5H, m)     488     1.53-1.99(6H, m), 2.30-3.24(14H, m), 3.55-4.12             (10H, m), 4.22-4.75(1H, m), 4.86-5.08(1H, m),             6.39-6.58(2H, m), 6.92-7.38(5H, m)     489     1.51-2.10(6H, m), 2.12-3.29(14H, m), 3.52-4.68             (11H, m), 4.77-5.07(1H, m), 6.35-6.62(2H, m),             6.92-7.48(5H, m)     490     1.55-2.00(6H, m), 2.34-3.25(14H, m), 3.53-4.72             (11H, m), 4.81-5.07(1H, m), 6.39-6.58(2H, m),             6.92-7.37(5H, m)     491     1.49-2.08(8H, m), 2.48-3.13(8H, m), 3.44(2H, t,             J=6.7Hz), 3.76-5.08(3H, m), 4.00(2H, t, J=6.3             Hz), 6.83-7.48(8H, m)     492     1.42-1.63(4H, m), 1.68-2.02(6H, m), 2.48-3.18             (8H, m), 3.43(2H, t, J=6.7Hz), 3.86-5.13(3H, m),             3.99(2H, t, J=6.3Hz), 6.84-7.52(8H, m)     493     0.98-2.02(18H, m), 2.23-3.13(12H, m), 3.85-497             (3H, m), 3.98(2H, t, J=6.4Hz), 6.83-7.47(8H, m)     494     1.42-1.95(9H, m), 2.22(1H, t, J=2.4Hz), 2.48-             3.13(10H, m), 3.43(2H, d, J=2.4Hz), 3.84-5.13             (3H, m), 3.99(2H, t, J=6.4Hz), 6.84-7.51(8H, m)     ______________________________________

Using the suitable starting materials, the following compounds are obtained in the same manners as in Examples 1, 384, 390-393, 398, 399, 407-409, 426 and 593.

                  TABLE 11     ______________________________________      ##STR785##     ______________________________________     Example 779     Structure      ##STR786##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 495)     Form: Free     Example 780     Structure      ##STR787##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 496)     Form: Free     Example 781     Structure      ##STR788##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 497)     Form: Free     Example 782     Structure      ##STR789##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 498)     Form: Free     Example 783     Structure      ##STR790##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 499)     Form: Free     Example 784     Structure      ##STR791##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 500)     Form: Free     Example 785     Structure      ##STR792##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 501)     Form: Free     Example 786     Structure      ##STR793##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 502)     Form: Free     Example 787     Structure      ##STR794##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 503)     Form: Free     ______________________________________

Using the suitable starting materials, the following compound is obtained in the same manners as in Examples 1, 384, 390-393, 398, 399, 407-409, 421 and 593.

                  TABLE 12     ______________________________________      ##STR795##     ______________________________________     Example 788     Structure      ##STR796##     R.sup.1 : H, q: 1     Bond between 3- and 4-positions in the     carbostyril ring: Single bond     NMR analysis: 504)     Form: Free     ______________________________________

                  TABLE 13     ______________________________________     No.      NMR (CDCl.sub.3) δ value     ______________________________________     495      1.66(9H, s), 1.42-1.93(8H, m), 2.51-3.22(11H,              m), 3.83-5.15(3H, m), 3.98(2H, t, J=6.4Hz),              6.83-7.48(8H, m)     496      0.93(6H, d, J=6.6Hz), 1.42-1.94(9H, m), 2.33-              3.14(11H, m), 2.46(2H, d, J=6.9Hz), 3.83-5.18              (3H, m), 3.98(2H, t, J=6.4Hz), 6.85-7.48(8H, m)     497      0.93(9H, s), 1.43-2.01(9H, m), 2.37(2H, s),              2.50-3.13(10H, m), 3.82-5.03(3H, m), 3.99(2H, t,              J=6.4Hz), 6.86-6.94(2H, m), 6.98-7.30(4H, m),              7.38-7.47(2H, m)     498      1.43-1.96(9H, m), 1.75(3H, s), 2.52-3.13(10H,              m), 3.19(2H, s), 3.88-5.05(3H, m), 3.99(2H, t,              J=6.4Hz), 4.85(2H, d, J=6.5Hz), 6.85-7.52(8H, m)     499      0.28-0.51(4H, m), 1.41-1.94(9H, m), 2.06-2.21              (1H, m), 2.51-3.17(10H, m), 3.82-5.08(3H, m),              3.98(2H, t, J=6.4Hz), 6.86-7.51(8H, m)     500      0.91(9H, s), 1.34-1.94(10H, m), 2.11(1H, brs),              2.49-3.12(12H, m), 3.84-5.03(3H, m), 3.98(2H, t,              J=3.4Hz), 6.83-7.48(8H, m)     501      0.91(3H, t, J=7.2Hz), 1.24-1.93(12H, m), 2.13              (1H, brs), 2.44-3.15(12H, m), 3.78-5.14(3H, m),              3.98(2H, t, J=6.4Hz), 6.84-7.48(8H, m)     502      1.39-1.95(8H, m), 2.11(3H, d, J=1.5Hz), 2.27              (3H, s), 2.33(3H, s), 2.48-3.13(16H, m), 3.26-              3.67(4H, m), 3.87-5.10(5H, m), 6.85-7.53(8H, m)     503      0.90(3H, t, J=7.4Hz), 1.07(3H, d, J=6.3Hz),              1.20-1.92(10H, m), 2.22(1H, brs), 2.49-3.12(11H,              m), 3.85-5.04(3H, m), 3.98(2H, t, J=6.4Hz),              6.83-7.48(8H, m)     504      1.02(6H, t, J=7.1Hz), 1.31-1.93(10H, m), 2.16-              3.13(15H, m), 3.49-3.67(1H, m), 3.85-4.93(3H,              m), 3.98(2H, t, J=6.4Hz), 6.83-7.48(8H, m)     ______________________________________

Reference Example 25

1,3-Cyclohexanedione (10.0 g) is dissolved in toluene (100 ml) with heating and thereto is added 4-amino-1-benzylpiperidine (18.6 ml). The mixture is refluxed for 2 hours by using Dean-Stark apparatus. After cooling, the precipitated crystal is washed with diethyl ether, and recrystallized from toluene to give 1-(1-benzyl-4-piperidinylamino)-1-cyclohexen-3-on (24.2 g) as light yellow prisms, m.p.: 171°-172° C.

Reference Example 26

Acrylic acid (28.9 ml) is added to 1-(1-benzyl-4-piperidinylamino)-1-cyclohexen-3-on (100 g) and the mixture is refluxed with stirring for 6 hours. After cooling, the reaction mixture is dissolved in chloroform containing 10% methanol and purified by silica gel column chromatography (solvent; dichloromethane:methanol=40:1). The resultant is recrystallized from ethanol/water to give 1-(1-benzyl-4-piperidinyl)-5-oxo-3,4,5,6,7,8-hexahydrocarbostyril (23.98 g) as colorless needles, m.p.: 102°-103° C.

Reference Example 27

1-(1-Benzyl-4-piperidinyl)-5-oxo-3,4,5,6,7,8-hexahydrocarbostyril (10.0 g) is dissolved in chloroform (500 ml) and thereto is added N-bromosuccinimide (5.78 g). The mixture is refluxed with stirring for 2 hours. Thereto are added N-bromosuccinimide (5.00 g) and triethylamine (50 ml) and the mixture is refluxed with stirring for 3 hours. After cooling, the reaction mixture is washed twice with 30% aqueous sodium thiosulfate solution (200 ml) and once with saline solution (500 ml) and then dried with magnesium sulfate. The solvent is evaporated off and the resulting residue is purified by silica gel column chromatography (solvent: dichloromethane:methanol=40:1) and recrystallized from ethanol/water to give 1-(1-benzyl-4-piperidinyl)-5-hydroxy-3,4-dihydrocarbostyril (2.13 g) as colorless needles, m.p.: 183°-184° C.

Reference Example 28

1-(1-Benzyl-4-piperidinyl)-5-hydroxy-3,4-dihydrocarbostyril (500 mg) is dissolved in acetone (20 ml) and thereto are added potassium carbonate (246 mg) and ethyl iodide (0.18 ml). The mixture is refluxed with stirring for 6.5 hours. After the reaction, the insoluble materials are removed by filtration, and the filtrate is concentrated under reduced pressure. Dichloromethane is added to the resulting residue and the mixture is washed with 5% aqueous sodium hydroxide solution and then dried with magnesium sulfate. The solvent is evaporated and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1) to give 1-(1-benzyl-4-piperidinyl)-5-ethoxy-3,4-dihydrocarbostyril (0.27 g).

NMR (CDCl₃) δ ppm: 1.41 (3H, t, J=7.0 Hz), 1.58-1.82 (2H, m), 2.03-2.24 (2H, m), 2.47-3.10 (8H, m), 3.54 (2H, s), 4.03 (2H, q, J=7.0 Hz), 4.19-4.36 (1H, m), 6.60 (1H, d, J=8.2 Hz), 6.85 (1H, d, J=8.2 Hz), 7.14 (1H, t, J=8.2 Hz), 7.22-7.37 (5H, m)

Reference Example 29

Using the suitable starting materials, N-(1-benzyl-4-piperidinyl)-3,5-dimethylaniline is obtained in the same manner as in the above Reference Example 1.

NMR (CDCl₃) δ ppm: 1.35-1.60 (2H, m), 1.95-2.20 (4H, m), 2.22 (6H, s), 2.70-2.94 (2H, m), 3.15-3.40 (1H, m), 3.52 (2H, s), 6.22 (2H, s), 6.33 (1H, s), 7.20-7.40 (5H, m)

Reference Example 30

Using the suitable starting materials, N-cinnamoyl-N-(1-benzyl-4-piperidinyl)-3,5-dimethylaniline is obtained in the same manners as in the above Reference Example 15 as white powders, m.p.: 151°-154° C.

Reference Example 31

Using the suitable starting materials; 1-(1-benzyl-4-piperidinyl)-5,7-dimethylcarbostyril hydrochloride is obtained in the same manner as in the above Reference Example 16 as white powders, m.p.: 241°-244° C.

Reference Example 32

Using the suitable starting materials, N-(1-benzyl-4-piperidinyl)-2-formyl-3-fluoroaniline is obtained in the same manner as in the above Reference Example 19 as yellow powders, m.p.: 108°-109° C.

Reference Example 33

Using the suitable starting materials, methyl 2-fluoro-5-[(1-benzyl-4-piperidinyl)amino]cinnamate is obtained in the same manner as in the above Reference Example 24 as white powders, m.p.: 130°-133° C.

Reference Example 34

Potassium carbonate (8.9 g), 4-amino-1-benzyl-piperidine (18.5 g), cupric oxide (0.6 g) and dimethylformamide (25 ml) are added to 2-chloro-6-fluorobenzoic acid (11.3 g) and the mixture is reacted with heating at 140° C. for 6 hours. After the reaction, the solvent is concentrated and to the resulting residue are added water (200 ml) and active carbon (1 g). The mixture is refluxed for 30 minutes. After filtration, the filtrate is cooled and then adjusted to pH 8.0 with diluted hydrochloric acid. The precipitated crystal is collected by filtration and washed successively with water and methanol to give 2-(1-benzyl-4-piperidinylamino)-6-fluorobenzoic acid (7.6 g) as white powders, m.p.: 233°-236° C.

Reference Example 35

To a solution of lithium aluminium hydride (0.9 g) in anhydrous tetrahydrofuran (160 ml) is added 2-(1-benzyl-4-piperidinylamino)-6-fluorobenzoic acid (8.0 g) and the mixture is refluxed for 1 hour. After cooling, the reaction solution is poured into ice-water and then extracted with dichloromethane. The solvent is concentrated and to the resulting residue is added diethyl ether/n-hexane. The precipitated crystal is collected by filtration to give N-(1-benzyl-4-piperidinyl)-2-hydroxymethyl-3-fluoroaniline (4.6 g) as light yellow powders, m.p.: 167°-170° C.

Pharmacological Test

Experiment 1: V₁ receptor binding assay

Using rat liver plasma membrane preparations prepared according to Ichihara's method [cf: Akira Ichihara, J. Bio. Chem., 258 9283 (1983)], the plasma membrane (50000 dpm, 2×10⁻¹⁰ M) of [H]³ -Arg-vasopressin and a test compound (100 ng, 10⁻⁷ -10⁻⁴ M) are incubated at 37° C. for 10 minutes in 100 mM Tris-HCl buffer pH: 8.0 (250 μl) containing 5 mM MgCl₂, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filtered three times using the glass filter (GF/F) so as to separate the membrane preparation combining with vasopressin and then washed with the buffer (5 ml). This glass filter is taken out and mixed with liquid scintillation cocktail. The amount of [H]³ -vasopressin combining with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation. ##EQU1##

C¹ : The amount of [H]³ -vasopressin combining with the membrane in the presence of the test compound (known amount).

C⁰ : The amount of [H]³ -vasopressin combining with the membrane in the absence of the test compound.

B¹ : The amount of [H]³ -vasopressin combining with the membrane in the presence of the excess amount of vasopressin (10⁻⁶ M).

The results are expressed as IC₅₀ values, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50%.

The results are shown in the following Table 14.

Test Compounds

1. 1-[1-(4-Methylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

2. 1-[1-(4-Dimethylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

3. 1-{1-[4-(4-Carbamoylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

4. 1-{1-[4-(4-Carbamoylmethylaminocarbonylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

5. 1-{1-[4-(3-Cyanopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

6. 1-{1-[4-(3-Amidinopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

7. 1-{1-[4-(3-Carbamoylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

8. 1-{1-[4-(3-Ethoxycarbonylmethylaminocarbonylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

9. 1-{1-[4-(3-Carbamoylmethylaminocarbonylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

10. Methyl N-[4-{4-[4-(1,2,3,4-tetrahydro-2-oxo-1-quinolyl)-1-piperidinylcarbonyl]phenoxy}]butanoyl-L-serinate

11. Methyl N-[4-{4-[4-(1,2,3,4-tetrahydro-2-oxo-1-quinolyl)-1-piperidinylcarbonyl]phenoxy}]butanoyl-L-alanate

12. 1-{1-[4-(5-Carbamoylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

13. 1-{1-[4-(5-Ethoxycarbonylmethylaminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

14. 1-{1-[4-(5-Carbamoylmethylaminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

15. 1-{1-[4-(7-Carbamoylheptyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

16. 1-{1-[4-(7-Carbamoylmethylaminocarbonylheptyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

17. 1-{1-[4-(3-Dimethylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

18. 1-{1-[4-(3-Benzylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

19. 1-{1-[4-[3-(Phthalimido-1-yl)propoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

20. 1-{1-[4-(3-Acetylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

21. 1-{1-[4-(3-Methoxycarbonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

22. 1-{1-[4-(3-Methylsulfonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

23. 1-[1-{4-[3-(3-Methylureido)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

24. 1-{1-[4-(4-Aminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

25. 1-{1-[4-(4-(N-Acetylglycylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

26. 1-{1-[4-(4-Formylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyri

27. 1-{1-[4-(4-Methoxycarbonylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

28. 1-{1-[4-(4-Methylsulfonylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

29. 1-{1-[4-(5-Aminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

30. 1-{1-[4-(5-Methylamino-4-hydroxypentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

31. 1-{1-[4-(5-Dimethylamino-4-hydroxypentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

32. 1-{1-[4-(3-Hydroxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

33. 1-{1-[4-(3-Acetoxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

34. 1-{1-[4-(3-Methylsulfonyloxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

35. 1-{1-[4-(3-Carbamoyloxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

36. 1-{1-[4-(4-Hydroxybutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

37. 1-{1-[4-(4-Acetoxybutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

38. 1-{1-[4-(4-Carbamoyloxybutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

39. 1-{1-[4-(5-Acetoxypentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

40. 1-[1-(4-Methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

41. 1-[1-(4-Ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

42. 1-[1-(4-Propoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

43. 1-[1-(4-Butoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

44. 1-[1-(4-Allyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

45. 1-[1-(4-Phenyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

46. 1-[1-(4-Acetoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

47. 1-[1-(2,4-Dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

48. 1-[1-(2-Methoxy-4-methylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

49. 1-[1-(2-Methoxy-4-dimethylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

50. 1-{1-[2,4-Bis(N,N-dimethylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

51. 1-{1-[2-(2-Oxooxazolydine-3-yl)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

52. 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

53. 1-[1-(2-Methoxy-4-methylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

54. 1-[1-(2-Methoxy-4-chlorobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

55. 1-[1-(2-Dimethylamino-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

56. 1-[1-(2-Ethylamino-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

57. 1-[1-(2-Propylamino-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

58. 1-{1-[2-(N-Methyl-N-ethylamino)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

59. 1-[1-(2-Ethoxy-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

60. 1-[1-(2-Hydroxy-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

61. 1-[1-(2-Acetoxy-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

62. 1-[1-(2-Allyloxy-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

63. 1-{1-[2-(3-Hydroxypropoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

64. 1-{1-[2-(3-Acetoxypropoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

65. 1-{1-[2-(3-Carbamoyloxypropoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

66. 1-{1-[2-(3-Methoxypropoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

67. 1-{1-[2-(3-Carbamoylpropoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

68. 1-{1-[2-(2-Hydroxyethoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

69. 1-{1-[2-(2-Acetoxyethoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

70. 1-{1-[2-(2-Methoxyethoxy)-4-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

71. 1-[1-(4-Bromobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

72. 1-[1-(4-Benzoylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

73. 1-[1-(4-Methylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

74. 1-[1-(4-Ethylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

75. 1-[1-(4-Methylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

76. 1-[1-(4-Propylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

77. 1-[1-(4-Butylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

78. 1-[1-(3,4-Dimethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

79. 6-Fluoro-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

80. 7-Fluoro-1-[1-(2-methoxy-4-methylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

81. 7-Methyl-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

82. 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]carbostyril

83. 1-(1-Tricyclo[3.3.1.1³,7 ]decanylcarbonyl-4-piperidinyl)-3,4-dihydrocarbostyril

84. 1-[1-(2-Methoxy-4-methylthiobenzoyl)-3-pyrrolidinyl]-3,4-dihydrocarbostyril

85. 1-{4-[N-(4-Methoxyphenyl)-N-benzylamidophenyl]-3,4-dihydrocarbostyril

86. 1-{1-[4-(3-[4-(4-Methoxyphenyl)-1-piperazinyl]propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

87. 1-{1-[4-(3-Allyloxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

88. 1-{1-[4-(3-Carbamoylpropylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

89. 1-{1-[4-(2-Ethylthioimidazol-1-yl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

90. 1-{1-[4-(N-Allyl-N-methylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

91. 1-{1-[4-(1-Pyrrolidinyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

92. 1-[1-{4-[3-(N-Methyl-N-benzoylamino)propoxy]-benzoyl}-4-piperidinyl}-3,4-dihydrocarbostyril

93. 1-[1-{4-[3-(4-Phenyl-1-piperazinyl)propoxy]-benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

94. 1-{1-[4-(3-Benzoyloxypropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

95. 1-{1-[4-(3-Ethylthiopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

96. 1-[1-(4-Propargylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

97. 1-[1-(4-Benzyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

98. 1-{1-[4-(2-Cyclohexenyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

99. 1-[1-(4-Cyclohexyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

100. 1-[1-(4-Methylsulfonyloxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

101. 1-[1-(4-Glycidoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

102. 1-{1-[4-Methoxy-2-(N-methyl-N-ethoxycarbonylmethylamino)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

103. 1-[1-(4-Methoxy-2-benzyloxycarbonylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

104. 1-[1-(4-Methoxy-2-acetylaminobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

105. 1-[1-(4-Methoxy-2-methylaminocarbonylmethylamino)-4-piperidinyl]-3,4-dihydrocarbostyril

106. 1-[1-(4-Trifluoromethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

107. 1-[1-(4-Acetylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

108. 1-[1-(4-Hydroxyiminomethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

109. 1-[1-(4-Methoxymethylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

110. 1-[1-(4-Trimethylsilylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

111. 1-[1-(4-Allylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

112. 1-[1-(4-Cyclohexylbenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

113. 1-[1-(3,4-Methylenedioxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

114. 1-[1-(2,6-Dimethyl-1,5-heptadiene-1-carbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril

115. 1-(1-(Tricyclo[3.3.1.1³,7 ]decanylacetyl-4-piperidinyl]-3,4-dihydrocarbostyril

116. 1-[1-(2-Naphthylcarbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril

117. 1-[1-(3-quinolylcarbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril

118. 1-[3-Methyl-1-(2,4-dimethoxycarbonyl)-4-piperidinyl]-3,4-dihydrocarbostyril

119. 1-[1-(3-Nitro-4-methoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

120. 6,7-Difluoro-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

121. 1-{1-[4-(3-Methylaminocarbonylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

122. 1-{1-[4-(4-Hydroxy-1-butenyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

123. 1-{1-[4-(4-Hydroxybutyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

124. 1-{1-[4-(4-Acetoxybutyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

125. 1-[1-{4-[4-(1-pyrrolyl)butoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

126. 1-[1-{4-[(4-Methylaminobenzoyl)aminobutoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

127. 1-{1-[4-(Ethylsulfinylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

128. 1-{1-[4-(6-Hydroxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

129. 1-{1-[4-(5-Carbamoyloxypentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

130. 1-{1-[4-(6-Acetoxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

131. 1-{1-[4-(6-Dimethylamino-5-hydroxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

132. 1-[1-{4-[3-(1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihyrocarbostyril.dihydrochloride.trihydrate

133. 1-[1-{4-[3-(4-Benzyl-1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril.dioxalate

134. 1-[1-{4-[3-(4-Acetyl-1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

135. 1-[1-{4-[3-(4-Anilinocarbonyl-1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

136. 1-[1-{4-[3-(4-Methyl-1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril.dioxalate

137. 1-[1-{4-[3-(4-Benzoylmethyl-1-piperazinyl)propoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril.dioxalate

138. 1-{1-[4-(3-[4-(2-Phenyl-2-hydroxyethyl)-1-piperazinyl]propoxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

139. 5,7-Difluoro-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

140. 1-{1-[4-(6-Aminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

141. 1-{1-[4-(6-Acetylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

142. 1-{1-[4-(6-Methylsulfonylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

143. 1-{1-[4-(3-Ethylsulfonylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

144. 1-{1-[4-(6-Diethylamino-5-hydroxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

145. 1-{1-[4-(3-Formylaminopropoxy)benzoyl]-4-piperidinyl}-7-fluoro-3,4-dihydrocarbostyril

146. 1-{1-[4-{5-[1-(S)-Carbamoyl-2-(4-hydroxyphenyl)]ethylaminocarbonylpentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

147. 1-{1-[4-{5-[1-(S)-Carbamoyl-2-methyl]propylaminocarbonylpentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

148. 1-{1-[4-(3-Dimethylaminocarbonylpropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

149. 1-{1-[4-{5-[1-(S)-Carbamoyl-2}4(1H)imidazoyl}]ethylaminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

150. 1-{1-[4-(5-[1-(S),3-Dicarbamoyl]propylaminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

151. 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]-7-fluorocarbostyril

152. 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3-carboxy-3,4-dihydrocarbostyril

153. 1-{1-[4-(5-[1-(S)-Carbamoyl-3-(methylthio)]propylaminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

154. 1-{1-[4-(5-(Imidazo[4,5-c]pyridine-2-yl)carbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

155. 1-[1-(2-Hydroxy-4-ethoxybenzoyl)-4-piperidinyl]-7-fluoro-3,4-dihydrocarbostyril

156. 1-{1-[4-[(4-Benzyl-1-piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

157. 1-{1-[4-[4-(1-Piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

158. 1-{1-[4-[4-(4-Methyl-1-piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

159. 1-{1-[4-[4-(4-Methylsulfonyl-1-piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

160. 1-{1-[4-[4-(4-Methoxycarbonyl-1-piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

161. 1-{1-[4-[4-(4-Benzyl-1-piperazinyl)carbonyloxybutoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

162. 1-{1-[4-[4-(4-Acetyl-1-piperazinyl)butoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

163. 1-{1-[4-[4-(1-Piperazinyl)carbonyloxybutoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

164. 1-{1-[4-[4-(Benzimidazol-1-yl)thiobutoxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

165. 1-{1-[4-{5-[(5-Benzyloxycarbonylamino)-1-(S)-methoxycarbonyl]pentylaminocarbonylpentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

166. 1-{1-[4-{5-[5-Amino-1-(S)-methoxycarbonyl]pentylaminocarbonylpentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

167. 1-{1-[4-(3-Isopentylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

168. 1-{1-[4-(3-Ethoxycarbonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

169. 1-{1-[4-(3-Phenylsulfonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

170. 1-{1-[4-(5-Hydroxy-6-benzylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

171. 1-{1-[4-(5-Hydroxy-6-aminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

172. 1-{1-[4-(5-Hydroxy-6-(4-benzyl-1-piperazinyl)hexyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

173. 1-{1-[4-(5-Hydroxy-6-(1-piperazinyl)hexyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

174. 1-{1-[4-(3-p-Toluenesulfonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

175. 5,7-Difluoro-1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]carbostyril

176. 1-{1-[4-(5-Acetoxy-6-acetylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

177. 1-{1-[4-(5-Hydroxy-6-acetylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

178. 1-{1-[4-(5-Hydroxy-6-(4-methyl-1-piperazinyl)hexyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

179. 1-{1-[4-(4-Dimethylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

180. 1-{1-[4-(4-Dimethylaminobutyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

181. 1-{1-[4-(3-Acetylaminoacetylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

182. 1-{1-[4-(3-[2-(Acetylamino)valerylamino]propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

183. 1-{1-[4-(3-Formylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

184. 1-{1-[4-(7-Hydroxy-8-diethylaminooctyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

185. 7-Fluoro-1-{1-[4-(5-Hydroxy-6-diethylaminohexyloxy)-2-methoxybenzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

186. 1-{1-[4-(4-Hydroxy-5-(1-pyrrolidinyl)pentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

187. 1-{1-[4-(7-Hydroxy-8-dimethylaminooctyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

188. 1-{1-[4-(4-(Hydroxy-5-(1-piperidinyl)pentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

189. 1-{1-[4-(4-Hydroxy-5-morpholinopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

190. 1-{1-[4-(5-(2-Hydroxy-3-diethylaminopropoxy)pentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

191. 1-{1-[4-(5-(2-Hydroxy-3-dimethylaminopropoxy)pentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

192. 1-{1-[4-(3-(2-Hydroxy-3-diethylaminopropoxy)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

193. 1-{1-[4-(3-(4-Aminobenzoylamino)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

194. 1-{1-[4-(4-(Benzimidazol-2-yl)sulfinylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

195. 1-{1-[4-(3-(α-N-Acetyl-(L)-glutaminyl)aminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

196. 1-{1-[4-(3-(4-Acetylaminobenzoyl)aminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

197. 1-{1-[4-(5-(3-Dimethylaminopropyl)aminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

198. 1-{1-[4-(3-Ethylaminocarbonylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

199. 1-{1-[4-(5-(2-Dimethylaminoethyl)aminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

200. 1-{1-[4-(5-(1-Benzyl-4-piperidinyl)aminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

201. 5,7-Difluoro-1-{1-[2-methoxy-4-(5-hydroxy-6-diethylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

202. 1-{1-[4-(5-Hydroxy-6-(1-pyrrolidinyl)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

203. 1-{1-[4-(5-Hydroxy-6-[N-(2-phenylethyl)-N-methylamino]hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

204. 1-{1-[4-(5-Hydroxy-6-[N-(2-hydroxyethyl)-N-methylamino]hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

205. 1-{1-[4-(5-Hydroxy-6-(4-phenyl-1-piperazinyl)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

206. 1-{1-[4-(7-Hydroxy-8-(1-pyrrolidinyl)octyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

207. 1-{1-[4-(3-(2-Acetylamino-4-methylthiobutyrylamino)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

208. 1-{1-[4-(3-[2-(R)-Acetylamino-2-(4(1H)imidazolyl)methylacetylamino]propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

209. 1-{1-[4-(3-(2-Acetylaminopropanoylamino)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

210. 1-{1-[4-(5-(4-Piperidinyl)aminocarbonylpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

211. 1-{1-[4-(3-[2-Benzyloxycarbonylamino-2α-(4-hydroxybenzyl)acetylamino)propoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

212. 1-{1-[4-(6-Carbamoyloxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

213. 1-{1-[4-(6-Diethylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

214. 1-{1-[4-(6-(1-Pyrrolidinyl)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

215. 1-{1-[4-(6-(1-Methyl-5-oxo-3-morpholino)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

216. 5-Methyl-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

217. 1-{1-[4-(5-Hydroxy-6-isopropylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

218. 1-{1-[4-(5-Hydroxy-6-[N-ethyl-N-(2-tetrahydropyranylmethyl)amino]hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

219. 1-{1-[4-(5-Hydroxy-6-[N-methyl-N-(2-hydroxy-2-phenylethyl)amino]hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

220. 1-{1-[4-(6-[2(S)-Hydroxymethyl-1-pyrrolidinyl]-5-hydroxy)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

221. 1-{1-[4-(3-(S)-{N-(Bezyloxycarbonyl)prolyl}aminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

222. 1-[1-{4-[3-(S)-{N,N'-Di(benzyloxycarbonyl)lysyl}aminopropoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

223. 1-[1-{4-[3-(S)-Tyrosylaminopropoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

224. 1-{1-[4-(3-(S)-Prolylaminopropoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

225. 1-[1-{4-(3-(R)-Valylaminopropoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

226. 1-[1-{4-(3-(S)-{N-(Benzyloxycarbonyl)seryl}aminopropoxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril

227. 1-{1-(4-[4-(4-Allyl-1-piperazinyl)butoxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

228. 1-{1-(4-[4-(2-Chloroacetylamino)butoxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

229. 1-{1-(4-[5-(2-Acetoxyacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

230. 1-{1-(4-[5-(2-Hydroxyacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

231. 1-{1-(4-[4-(4-Piperidinylcarbonylamino)butoxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

232. 1-{1-(4-[4-(1-Acetyl-4-piperidinylcarbonylamino)butoxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

233. 1-{1-(4-[5-(4-[2-Pyrimidyl]-1-piperazinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

234. 1-{1-(4-[5-(4-[2-Pyridyl]-1-piperazinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

235. 1-{1-[4-(5-Triethylammouniumpentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril bromide

236. 1-{1-(4-[5-(4-(1-Imidazolyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

237. 1-{1-(4-[5-(4-(1,2,4-Triazol-1-yl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

238. 1-{1-(4-[5-(2-(S)-Hydroxymethyl-1-pyrrolidinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

239. 1-{1-(4-[5-(2-(S)-Methoxycarbonyl-1-pyrrolidinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

240. 1-{1-(4-[5-(3-Hydroxy-1-piperidinyl)-pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

241. 1-{1-(4-[5-(2-Hydroxymethyl-1-piperidinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

242. 1-{1-(4-[5-(4-Methyl-1-piperidinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

243. 1-{1-(4-[6-(1-Piperidinyl)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

244. 1-{1-(4-[5-(N-(2-Hydroxyethyl)-N-methylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

245. 1-{1-(4-[5-(N-Allyl-N-methylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

246. N-{5-[4-(4-(3,4-Dihydrocarbostyril-1-yl)-1-piperidinylcarbonyl)phenoxy]pentyl{, N-methyl, N-allylamine oxide

247. 1-{1-(4-[5-(N-(2-Cyanoethyl)-N-methylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

248. 1-{1-(4-[5-(N-(2-Dimethylaminoethyl)-N-benzylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

249. 1-{1-(4-[5-(N,N-Di(2-acetoxyethyl)amino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

250. 1-{1-(4-[5-(4-Benzyloxycarbonylaminobutyrylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

251. 1-{1-(4-[5-(2-Allylaminoacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

252. 1-{1-(4-[5-(2-(1-Pyrrolidinyl)acetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

253. 1-{1-(4-[5-(2-Morpholinoacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

254. 1-{1-(4-[5-(2-(4-Methyl-1-piperazinyl)acetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

255. 1-{1-(4-[5-(2-(4-Phenyl-1-piperazinyl)acetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

256. 1-{1-(4-[5-(2-Benzylaminoacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

257. 1-{1-(4-[5-(2-(N-(2-Hydroxyethyl)-N-methylamino)acetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

258. 1-{1-(4-[5-(4-Dimethylaminophenylsulfonylamino)pentyloxy]benzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

259. 1-{1-(4-[5-(4-Acetylaminobenzoyl)aminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

260. 1-{1-(4-[5-(3,4-Dihydroxycyclohexylcarbonylaminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

261. 1-{1-(4-[5-(3,4-Diacetoxycyclohexylcarbonyl)aminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

262. 1-{1-(4-[5-(4-Aminobenzoyl)aminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

263. 1-{1-(4-[5-(4-Nitrophenylsulfonyl)aminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

264. 1-{1-(4-[5-(4-Aminophenylsulfonyl)aminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

265. 1-{1-(4-[6-(4-(1-Piperidinyl)-1-piperidinyl)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril.dioxalate

266. 1-{1-(4-[6-(N-(2-(2-Pyridyl)ethyl)-N-methylamino)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

267. 1-{1-(4-[6-(N-(2-Methoxy-3,4,5-trihydroxytetrahydropyran-2-yl)methylamino)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

268. 1-{1-(4-[7-(Diethylamino)heptyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

269. 1-{1-(4-[5-(4-Benzyl-1-piperazinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

270. 1-{1-(4-[5-(1-Piperazinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

271. 1-{1-(4-[5-(4-Acetyl-1-piperazinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

272. 1-{1-(4-[5-(4-Methyl-1-piperazinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

273. 1-{1-(4-[5-(4-Allyl-1-piperazinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

274. 1-{1-(4-[5-(4-Carboxy-1-piperidinylcabonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

275. 1-{1-(4-[5-(4-Carbamoyl-1-piperidinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

276. 1-{1-(4-[5-(4-Dimethylaminocarbonyl-1-piperidinylcarbonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

277. 1-{1-[4-(8-Acetylaminooctyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

278. 1-{1-(4-[5-(1-Methyl-2-imidazolylthio)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

279. 1-{1-(4-[5-(2-Pyrimidylthio)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

280. 1-{1-(4-[5-(2-Pyrimidylsufinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

281. 1-{1-(4-[5-(2-Pyrimidylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

282. 1-{1-(4-[5-(1-Methyl-2-imidazolylsulfonyl)pentyloxy)benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

283. 1-{1-(4-[5-(4-Pyridylthio)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

284. 1-{1-(4-[5-(4-Aminophenylthio)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

285. 1-{1-(4-[5-(4-Nitrophenylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

286. 1-{1-(4-[5-(4-Aminophenylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

287. 1-{1-(4-[5-(2-Pyridylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

288. 1-{1-(4-[5-(Pyridine-N-oxide-4-ylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

289. 1-{1-(4-[5-(4-Acetylaminophenylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

290. 1-{1-(4-[5-(4-Dimethylaminophenylsulfonyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

291. 1-{1-(4-[2,4-Di(5-(1-pyrrolidinyl)pentyloxy]benzoyl)-4-piperidinyl}-3,4 -dihydrocarbostyril

292. 1-{1-[2,4-Di(5-diethylaminopentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

293. 1-{1-[2-Methoxy-4-(4-thiomorpholinocarbonylbutyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

294. 1-{1-[2-Methoxy-4-(4-carbamoylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

295. 1-{1-(2-Methoxy-4-[4-(4-oxothiomorpholino)carbonylbutyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

296. 1-{1-(2-Methoxy-4-[4-(4,4-dioxothiomorpholino)carbonylbutyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

297. 1-{1-[4-(5,6-Dihydroxyhexyloxy)benzoyl]piperidinyl}-3,4-dihydrocarbostyril

298. 1-{1-(4-[5-Hydroxy-6-(3-methoxybenzylamino)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

299. 1-{1-(4-[5-Hydroxy-6-(3,4-dimethoxybenzylamino)hexyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril.oxalate

300. 1-{1-(4-[5-Hydroxy-6-(N-methyl-N-(2-(2-pyridyl)ethyl)amino)hexyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

301. 1-{1-[4-(5-Methoxy-6-diethylmethylammoniumhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril.iodine

302. 1-{1-[4-(5-Hydroxy-6-(2-(S)-carbamoyl-1-pyrrolidinylhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

303. 1-{1-[4-(5-Hydroxy-6-(1-piperidinyl)hexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

304. 1-{1-(4-[5-Hydroxy-6-(4-benzyl-1-piperidinyl)hexyloxy]benzoyl]-piperidinyl}-3,4-dihydrocarbostyril

305. 1-{1-[4-(5-Acetoxy-6-diethylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

306. 5-Fluoro-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

307. 5-Methyl-1-{1-[4-(6-diethylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

308. 5-Hydroxy-1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

309. 5-Acetoxy-1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril

310. 1-{1-(4-[5-(2-Methanesulfonylaminoacetylamino)pentyloxy]benzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

311. 7-Fluoro-1-[1-(2,4-dimethoxybenzoyl)-4-piperidinyl}-3,4-dihydrocarbostyril

312. 1-{1-[4-(5-Acetylaminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

313. 1-{1-[4-(4-Acetylaminobutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril

                  TABLE 14     ______________________________________             Test             Comp. IC.sub.50             No.   (μM)     ______________________________________              1    0.4              2    0.5              3    0.33              4    0.24              5    0.49              6    0.47              7    0.31              8    0.3              9    0.35              10   0.32              11   0.30              12   0.23              13   0.28              14   0.16              15   0.26              16   0.15              17   0.43              18   0.27              19   0.5              20   0.44              21   0.36              22   0.34              23   0.24              24   0.33              25   0.24              26   0.25              27   0.27              28   0.16              29   0.28              30   0.33              31   0.25              32   0.46              33   0.45              34   0.25              35   0.15              36   0.37              37   0.36              38   0.27              39   0.15              40   0.5              41   0.2              42   0.3              43   0.4              44   0.3              45   0.2              46   0.5              47   0.1              48   0.4              49   0.2              50   0.4              51   0.49              52   0.08              53   0.08              54   0.27              55   0.2              56   0.33              57   0.27              58   0.45              59   0.2              60   0.2              61   0.3              62   0.15              63   0.27              64   0.46              65   0.27              66   0.41              67   0.47              68   0.36              69   0.42              70   0.32              71   0.5              72   0.48              73   0.2              74   0.18              75   0.5              76   0.3              77   0.35              78   0.4              79   0.5              80   0.08              81   0.21              82   0.33              83   0.5              84   7.1              85   3              86   0.57              87   0.53              88   1.0              89   1.6              90   1.1              91   0.72              92   1.2              93   0.64              94   0.63              95   0.96              96   0.6              97   1.1              98   0.77              99   0.96             100   0.9             101   1.6             102   1.1             103   0.7             104   1.0             105   1.2             106   0.7             107   0.75             108   1.4             109   0.75             110   1.3             111   0.73             112   0.97             113   0.98             114   1.5             115   0.7             116   0.76             117   1.5             118   0.26             119   1.4             120   0.2             121   0.46             122   0.71             123   0.35             124   0.32             125   0.59             126   0.36             127   0.61             128   0.23             129   0.18             130   0.39             131   0.066             132   0.16             133   0.33             134   0.16             135   0.2             136   0.18             137   0.12             138   0.24             139   0.051             140   0.1             141   0.12             142   0.1             143   0.55             144   0.022             145   0.17             146   0.073             147   0.098             148   0.36             149   0.15             150   0.096             151   0.16             152   1.6             153   0.084             154   0.2             155   0.057             156   0.18             157   0.09             158   0.10             159   0.098             160   0.22             161   0.45             162   0.11             163   0.075             164   0.78             165   0.54             166   0.044             167   0.28             168   0.19             169   0.17             170   0.039             171   0.24             172   0.043             173   0.039             174   0.49             175   0.32             176   0.13             177   0.13             178   0.045             179   0.25             180   0.40             181   0.23             182   0.12             183   0.24             184   0.039             185   0.01             186   0.063             187   0.040             188   0.068             189   0.13             190   0.033             191   0.034             192   0.061             193   0.12             194   0.35             195   0.19             196   0.17             197   0.035             198   0.32             199   0.055             200   0.034             201   0.008             202   0.027             203   0.049             204   0.059             205   0.12             206   0.03             207   0.07             208   0.10             209   0.25             210   0.023             211   0.25             212   0.16             213   0.059             214   0.058             215   0.17             216   0.041             217   0.053             218   0.044             219   0.060             220   0.020             221   0.25             222   0.65             223   0.072             224   0.094             225   0.099             226   0.48             227   0.13             228   0.20             229   0.20             230   0.18             231   0.041             232   0.12             233   0.21             234   0.18             235   0.066             236   0.26             237   0.075             238   0.033             239   0.15             240   0.048             241   0.021             242   0.059             243   0.039             244   0.034             245   0.054             246   0.29             247   0.17             248   0.034             249   0.045             250   0.32             251   0.098             252   0.086             253   0.18             254   0.060             255   0.38             256   0.19             257   0.20             258   0.47             259   0.11             260   0.15             261   0.12             262   0.093             263   0.36             264   0.16             265   0.019             266   0.035             267   0.082             268   0.027             269   0.16             270   0.044             271   0.042             272   0.038             273   0.057             274   0.49             275   0.046             276   0.11             277   0.30             278   0.11             279   0.18             280   0.087             281   0.054             282   0.075             283   0.61             284   0.40             285   0.23             286   0.15             287   0.10             288   0.048             289   0.10             290   0.30             291   0.098             292   0.077             293   0.22             294   0.17             295   0.077             296   0.073             297   0.52             298   0.065             299   0.065             300   0.034             301   0.047             302   0.088             303   0.038             304   0.037             305   0.065             306   0.084             307   0.023             308   0.095             309   0.073             310   0.16     ______________________________________

Experiment 2: Anti-vasopressor activity in vivo

The spinal cord of male SD rat (weighing 300-400 g) is broken to give a pith rat. The blood pressure of the pith rat is measured through the cannula inserted into the femoral artery thereof by using a pressure transducer. The test compound and Arg-vasopressin are administered to the pith rat through the cannula inserted into the femoral vein. Anti-vasopressor activity of the test compound in vivo is determined according to the following equation. ##EQU2## P₀ : The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenously.

P: The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenouly 3 minutes after the intravenous administration of the test compound.

The results are expressed as ED₅₀ value, which is the dose of the test compound required to reduce the increase of diastolic pressure caused by the intravenous administration of Arg-vasopressin (30 mU/kg) to 50% of its control value: P⁰.

The results are shown in the following Table 15.

                  TABLE 15     ______________________________________     Test      ED.sub.50    Test      ED.sub.50     Comp. No. (mg/kg)      Comp. No. (mg/kg)     ______________________________________      2        1.0           47       0.4     20        0.2          311       0.3     40        0.8          312       0.8     41        0.5          313       0.3     ______________________________________ 

What is claimed is:
 1. A carbostyril derivative of the following formula: ##STR797## wherein R¹ is hydrogen; nitro; a lower alkoxy; a lower alkoxycarbonyl; a lower alkyl; a halogen; an amino having optionally one or two substituents selected from a lower alkanoyl, a lower alkyl, benzoyl and a phenyl(lower)alkoxycarbonyl; hydroxy; cyano; carboxy; a lower alkanoyloxy; or a hydrazinocarbonyl, q is an integer of 1 to 3 and q is 1 when R¹ is hydrogen and R is a group of the formula: ##STR798## R¹⁰ is a group of the formula: ##STR799## wherein l is 1 and R¹¹ and R¹² are the same or different and are each hydrogen, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, a benzoyl which may optionally have a lower alkoxy as a substituent, tricyclo(3.3.1.1)decanyl, a phenyl which may optionally have a lower alkoxy as a substituent, or a cycloalkyl, or R¹¹ and R¹² may bind together with the nitrogen atom to which they bond to form a saturated or unsaturated heterocyclic group selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroquinolyl, indolyl, isoindolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1H-indazolyl, 1,2-dihydroquinazolyl, 1,2-dihydrocinnolyl, 1,2-dihydroquinoxalyl, 1,2,3,4-tetrahydroquinazolyl, 1,2,3,4-tetrahydrocinnolyl and 1,2,3,4-tetrahydroquinoxalyl, wherein the heterocyclic group may optionally have a substituent selected from benzoyl, a lower alkanoyl, a phenyl(lower)alkyl and a phenyl which may optionally be substituted with a lower alkoxy and a lower alkanoyl, and the bond between the 3-position and the 4-position of the carbostyril ring is a single bond or double bond, or a salt thereof.
 2. The compound according to claim 1, wherein the bond between the 3- and 4-positions of the carbostyril nucleus is a single bond, and a salt thereof.
 3. The compound according to claim 1, wherein the bond between the 3- and 4-positions of the carbostyril nucleus is a double bond, and a salt thereof.
 4. The compound according to claim 1, wherein R¹ is hydrogen or a halogen, and a salt thereof.
 5. A vasopressin antagonistic composition which comprises as an active ingredient a compound of the formula (1) as set forth in claim 1, or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or diluent.
 6. The compound according to claim 1, wherein l is 1, and R¹¹ and R¹² are the same or different and are each hydrogen, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, a benzoyl which may optionally have a lower alkoxy as a substituent, tricyclo[3.3.1.1]decanyl, a phenyl which may optionally have a lower alkoxy as a substituent, or a cycloalkyl, or a salt thereof.
 7. The compound according to claim 1, wherein l is 1 and R¹¹ and R¹² may bind together with the nitrogen atom to which they bond to form a saturated or unsaturated heterocyclic group selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, oxazolinyl, oxazolidinyl, isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroquinolyl, indolyl, isoindolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1H-indazolyl, 1,2-dihydroquinazolyl, 1,2-dihydrocinnolyl, 1,2-dihydroquinoxalyl, 1,2,3,4-tetrahydroquinazolyl, 1,2,3,4-tetrahydrocinnolyl and 1,2,3,4-tetrahydroquinoxalyl, wherein the heterocyclic group may optionally have a substituent selected from benzoyl, a lower alkanoyl, a phenyl(lower)alkyl and a phenyl which may optionally be substituted with a lower alkoxy and a lower alkanoyl, or a salt thereof.
 8. The compound according to claim 7, wherein R¹¹ and R¹² may bind together with the nitrogen atom to which they bond to form piperazinyl, piperidinyl and 1,2,3,4-tetrahydroquinolyl, or a salt thereof.
 9. The compound according to claim 6, wherein R¹¹ and R¹² are the same or different and are each hydrogen, a lower alkyl, a phenyl(lower)alkyl, a lower alkenyl, or a phenyl which may optionally have a lower alkoxy as a substituent, or a salt thereof.
 10. The compound according to claim 1, wherein R¹ is a hydrogen atom, or a hydrochloride salt thereof. 